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Anticancer gene
Cite this page From Wikipedia, the free encyclopedia
Wikidata item
Anticancer genes are genes that, when ectopically overexpressed, specifically destroy tumour cells without harming normal,
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untransformed cells. This cellular destruction can be due to a variety of mechanisms, such as apoptosis, mitotic catastrophe followed by
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 Printable version apoptosis or necrosis, and autophagy. Anticancer genes emerged from studies on cancer cells in the late 1990s. Currently, there have
been 291 anticancer genes discovered in the human genome. In order to be classified as an anticancer gene, the gene must have base
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substitutions leading to missense amino-acid changes, deletions, or insertions leading to frameshifts that alter the protein the gene codes
‫اﻟﻌﺮﺑﯿﺔ‬
Edit links for, increases and decreases in copy-number increases, or gene rearrangements leading to their deregulation.[1]

Contents [hide]
1 Anticancer genes as therapeutics
2 Summary of anticancer genes
3 Common anticancer gene examples
3.1 APOPTIN
3.1.1 History
3.1.2 Action
3.2 Brevinin-2R
3.2.1 History
3.2.2 Action
3.3 E4orf4
3.3.1 History
3.3.2 Action
3.4 HAMLET
3.4.1 History
3.4.2 Action
3.5 MDA-7
3.5.1 History
3.5.2 Action
3.6 NOXA
3.6.1 History
3.6.2 Action
3.7 NS1
3.7.1 History
3.7.2 Action
3.8 ORCTL3

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 3.8.1 History
3.8.2 Action
3.9 Par-4
3.9.1 History
3.9.2 Action
3.10 TRAIL
3.10.1 History
3.10.2 Action
3.11 TP53
3.11.1 History
3.11.2 Action
4 Common misconceptions
5 See also
6 References

Anticancer genes as therapeutics [ edit ]

Main article: Gene therapy for cancer

Cancer is classified as a group of diseases, all of which are characterized by uncontrolled cell proliferation.[2] In normal functioning cells,
apoptosis is induced to avoid these proliferative events. However, these processes may continue on to become cancer in the event the
processes become dysregulated. Epidemiological studies have shown cancer to be a leading cause of death worldwide [2] (Figure 1).
Current advancements in therapeutics have led to a substantial increase in patient survival rates. Below is a non-comprehensive list of
common anticancer genes.

Summary of anticancer genes [ edit ]

Anti- Subcellular
Functional Blocked by Caspases Activated by Engaging cell Type of
cancer localization in cancer
p53 required Bcl-2 involved phosphorylation death pathway cell death
gene cells
Apoptin No No Yes Yes Intrinsic Nucleus Apoptosis

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 Brevinin- Undetermined Yes No Undetermined Intrinsic Cytoplasm Autophagy
2R
Mitotic
E4orf4 No No No Yes Intrinsic Nucleus, cytoplasm
catastrophe
Nucleus, ER, Apoptosis,
HAMLET No No Yes No Intrinsic
mitochondria autophagy
MDA-7 No Yes Yes No Intrinsic Receptor-binding, ER Apoptosis
Noxa No Yes Yes Undetermined Intrinsic Mitochondria Apoptosis
NS1 No No No Yes Intrinsic Cytoplasm Apoptosis
Plasma membrane,
ORCTL3 Undetermined Undetermined Yes Undetermined Intrinsic Apoptosis
ER, golgi
Extrinsic, Nucleus, ER, plasma
PAR-4 No No Yes Yes Apoptosis
Intrinsic membrane
TRAIL No Yes Yes No Extrinsic Receptor-binding Apoptosis

[3]

Common anticancer gene examples [ edit ]

APOPTIN [ edit ]

History [ edit ]

Apoptin was the first anticancer gene to be isolated.[citation needed] This gene comes from the single, circular minus-strand DNA found in
the Chicken Anemia Virus (CAV) genome.[4] This virus belongs to the Gyrovirus genus, and is currently being studied as a new cancer
therapeutic and diagnostic tool. This protein, also known as viral protein 3 (VP3) was isolated from chickens, and has been shown to
cause PCD in transformed human cells.

Action [ edit ]

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 This protein encoded for by Apoptin has the specific capability of attacking transforming cells while leaving untransformed cells
unharmed. Independent of p53, Apoptin induces apoptosis through an intrinsic, mitochondrial pathway. And unlike other PCD pathways,
the pathway of Apoptin is independent of death receptors.[citation needed] In normal functioning cells, this 13.6-kDa protein resides in the
cytoplasm, yet in cancerous cells, it travels to the nucleus via phosphorylation at the Thr-108 position via the mitogenic cyclin dependent
kinase (CDK2).[citation needed] Additionally, this protein does not act alone. Several Apoptin-interacting molecules are needed in order for
Apoptin to be fully functional. These molecules include, but not limited to, DNA, clyclinA-CDK2, and fas-associated death domain protein
(FADD).[citation needed] Current apoptin therapeutic agents have been used to treat Lewis lung carcinomas, and osteosarcomas with future
implications in treating liver cancers.[4]

Brevinin-2R [ edit ]

History [ edit ]

Brevinin-2R is a peptide product isolated from the skin of the frog Rana ridibunda (Figure 2).[5]
This non-hemolytic defensin has been shown to have preferential cytotoxicity towards various
cancer cells including B-cell lymphoma, colon carcinomas, lung carcinomas, and breast
adenocarcinoma.[6] Currently, this peptide and two of its analogs, Brevinin-2R-C and Brevinin-
2R-D, are being explored for cancer drug development.[7] A phylogenetic analysis shows that
Brevinin-2 is segregated into three major clades: A, B and C, where clade A contains the
Brevining-2R homolog.[6]

Action [ edit ]

This 25 amino acid peptide, in contrast to the majority of peptides within the Brevinin family, has
low hemolytic action.[7] Not only does the peptide have a reduced hemolytic action, it also is
Figure 2 Depiction of Rana
semi-selective towards cancer cells and leaves non cancerous cells largely unharmed. This ridibunda.
peptide works as to prevent the progression of cancer by arresting the cell cycle at the G2/M
phase, resulting in an induction of apoptosis.[7]

This defensin traditionally works as a part of the innate immune system, working as an antimicrobial defense.[8] However, this peptide is
currently being studied as an anticancer peptide. Brevinin-2R works to trigger cell death by reducing the mitochondrial membrane
potential resulting in lower cellular ATP levels while simultaneously increasing the concentration of reactive oxygen species.[8] Currently
and somewhat unrelated, Brevinin-2R is being considered for diabetic treatments. In treating type II diabetes, or diabetes mellitus,

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 Brevinins have been shown to promote insulin release. Finally, these peptides even have the capability to increase the rate of tissue
regeneration, as seen with the frog in which Brevinin-2R was isolated from.[8]

E4orf4 [ edit ]

History [ edit ]

Early region 4 open-reading-frame 4 (E4orf4) is an adenovirus protein of 14kDa which regulates growth in all stages of the adenovirus
(Ad) infection. E4orf4 partners mainly with protein phosphatase 2A (PP2A) and Src kinases to induce cell death. Modeling of this protein
reveals that it is likely made up of 3 α-helices with N- and C-terminal loops. It has a small stretch of amino acids in positions 66–75, which
are highly basic, and likely are a place of nuclear and nucleolar targeting, as well as a place for Src kinases to bind.[9]

Action [ edit ]

E4orf4 is an important regulator of adenoviruses. Additionally, outside of the context of the virus, it causes programmed cell death both in
the context of a healthy cellular environment, and cancer. E4orf4 is a key regulator of Ad by down-regulating both viral and cellular genes,
which plays an important role in regulating the proliferation of the virus. In turn, the down-regulation also impacts the alternative splicing
of the viral RNA and protein translation. In the absence of a viral infection, E4orf4 induces apoptosis in a p53 and caspase-independent
manner; however, there is still communication between this pathway and the caspase-dependent apoptosis pathway. In the context of
cancer, E4orf4 is even more efficient at inducing cell death than in healthy cells, which could be an important finding for potential cancer
therapies. It has been discovered that the mechanisms behind the function of E4orf4 is closely associated with several other proteins
including the B55 subunit of PP2A. E4orf4 binds to PP2A to reduce the phosphorylation of the DNA damage response (DDR) proteins.
Consequently, this reduces the function of DDR and limits DNA repair. Many cancer cells have defects in the DDR pathways and
targeting these cells with E4orf4 can potentially destroy the remaining DDR pathways, resulting in cancer cell death.[10]

The main mechanism behind the specificity of cancer cell targeting by E4orf4 is unknown but there are multiple hypotheses that scientists
are considering: 1) The activation of the oncogenic state causes dormant apoptotic signals to be initiated and cause cell death to be more
easily achieved by different signals. 2) There has been some indication that cancer cells become addicted to oncogenic pathways. E4orf4
may inhibit these pathways, causing cell death in cancer cells, but not normal cells. 3) E4orf4 may use oncogenes that have been
activated in cancer cells, including Src, to cause cell death. 4) Cancer cells have disrupted cell cycle checkpoints and E4orf4 can take
advantage of this by disrupting checkpoints in mitosis. 5) A Drosophila model demonstrated that E4orf4 can inhibit classical apoptosis in
healthy tissues. It has been considered that this function of E4orf4 is lost in cancer cells causing a more effective killing of cells. 6) E4orf4

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 has been shown to cause structural changes in mitochondria, which could impact metabolic reprogramming and may affect cancer and
healthy cells differently.[9]

HAMLET [ edit ]

History [ edit ]

HAMLET is known as an anticancer protein complex found in breast milk. One of the
two molecules of this complex is multimeric alpha lactalbumin (MAL) (Figure 3), which
was first discovered during a study in 1995 that investigated how breast milk affects
bacteria transformed with lung cancer. This study found that transformed cells were
selected for apoptosis at a much higher rate than the untransformed, healthy cells.[11] A
later study in 2000, ascertained that oleic acid, a C18:1 fatty acid, is a cofactor that
binds to MAL forming HAMLET. This complex, in a partially unfolded state, then
Figure 3: Crystal Structure of Calcium-bound
displays apoptotic activity in cancer cells.[12]
α-lactalbumin.

Action [ edit ]

Apoptosis, or programed cell death, can occur through activation of three different pathways, intrinsic, extrinsic, or tumor necrosis factor.
HAMLET proceeds by both a multifaceted intrinsic pathway and the caspase cascade, a subsection of the TNF pathway, through
targeting many different cell components.[13] First, after uptake by the cell, HAMLET proceeds to the mitochondria and depolarize the
membranes at cytochrome c. Consequently, mitochondria dependent apoptosis factors are released as well as the caspase cascade is
activated.[14] Second, proteasomes are targeted by HAMLET through a mechanism that is less understood. Research does suggest that
HAMLET directly binds to the proteasome leading to its inhibition.[15] Third, HAMLET has been found to target the nucleus, specifically
histones. HAMLET irreversibly binds to histones leading to the inactivation of transcription and chromatin condensation, which inevitably
causes apoptosis.[16] Lastly, studies show that cells treated by HAMLET exhibit behaviors common to macroautophagy. This includes
presence of cytoplasmic vacuoles, double-membrane vesicles, and a dose-dependent decrease in ATP levels.[13]

MDA-7 [ edit ]

History [ edit ]

Melanoma differentiation associated gene-7 (mda-7), and also known as IL-24, was discovered in the mid-1900s using subtraction
hybridization. mda-7 is classified in the interleukin IL-10 family because of similar structure and amino acid sequence to other interleukins

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 in that class, the chromosomal location (human chromosome 1q32-33),[17] and the shared properties it has with cytokines. Protein
structural studies reveal that it is a dimer and glycolsylated. It has been found that its expression is either not present or present at very
low levels in tumor cells, including advanced stage melanoma and metastatic disease, compared to normal non-transformed cells.
Multiple studies within the past 15 years have demonstrated that increasing mda-7 expression in tumor cells results in growth arrest and
cell death in many different cell lines. When mda-7 is over-expressed in normal cells, no change in growth or cell viability is detected.
mda-7 is also considered a radio-sensitizing cytokine because it generates a reactive oxygen species and causes stress in endoplasmic
reticulum.[18] mda-7 has been used in several clinical trials because of its ability to induce apoptosis, prevent tumor angiogenesis, cause
immune-regulation, and increase radiation lethality. It was seen in one Phase I clinical trial that injecting mda-7 via an adenovirus directly
into a tumor resulted in safe tumor regulation and immune activation.[18]

Action [ edit ]

mda-7 interacts with two of the type II cytokine hetero-dymeric receptor complexes IL-20R1/IL-20R2 and IL-22R1/IL-20R2. It has been
seen that in some contexts, mda-7 activates STAT transcription factors. However, the STAT pathway is not always activated and is not
required for mda-7 cell growth arrest and cell death. mda-7 can be placed into tumor cell lines via transfection or adenovirus-transduction;
it has been seen that following this, apoptosis is induced only in the tumor cells and results in no toxicity in the healthy cells.[17] Its
function as a tumor suppressor is not fully understood, but it has been observed that in the context of melanoma, mda-7 expression is
drastically decreased. While there are no official studies published backing this claim, it is thought that mda-7 could potentially act as a
paracrine factor, be involved in signaling short-range, and immune function in skin. mda-7 is also thought to have a pro-inflammatory
purpose. It is also possible that mda-7 induces cytokine secretion, which causes antigen-presenting cells to present tumor antigens,
resulting in an immune response against tumors. It has also been discovered that mda-7, and its translated protein MDA-7, interacts with
kinases including serine/threonine protein kinase (PKR).[17] Further studies will need to be performed to better understand the
mechanisms of mda-7 action.

NOXA [ edit ]

History [ edit ]

Noxa, isolated from mice, is a member of the Bcl-2 family and is able to regulate cell death through a variety of intracellular stress
signals.[19] Having been discovered nearly three decades ago in 1990 by Hijikata et al., this gene product was isolated this protein from
an adult T-cell leukemia (ATL) library[20] This gene, and its protein in which it encodes for, has been studied as a potential therapeutic in
chronic lymphocytic leukemia (CLL), the most common leukemia found in adults in the Western world.[19] In humans, the Noxa
homologue is known as APR/PMAIP1.[20]

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 Action [ edit ]

Upon receiving intrinsic death signals, the gene NOXA encodes for the
protein Noxa through a three-exon transcript.[20] This protein binds to anti-
apoptotic proteins resulting in these proteins' inhibition.[19] As a p53 inducible
gene, NOXA is transcribed and translated to Noxa in response to DNA
damage and hypoxia induced apoptosis.[19] A constitutive gene found in the
brain, thymus, spleen, and several other organs, it initiates apoptosis through
Bax-mediated mitochondrial-dysfunction through the inhibition of the Bcl2
family's antiapoptotic members.[20] Through gene knockout studies, it was
shown that double deficient Noxa there was no spontaneous tumor
development as commonly observed with knockout of p53.[20] Noxa has been
shown to be involved in the maintenance of memory CD4+ T Th1/Th2 cell
Figure 4: Depiction of T-Cells, T-Helper Cells, and B-
homeostasis where in the absence of Noxa, Th2 memory T-cell death Cells (CD4+) working to illicit an immune response.
results.[20]

NS1 [ edit ]

History [ edit ]

In the 1960s rodent parvovirus was discovered by Dr. Helene Toolan to have an oncosuppressive activity.[21][22][23][24][25] However, the
specific gene found in the parvovirus genome, which is called NS1, that causes the oncosuppressive activity was not characterized until
later. NS1 is a small protein (only 672 amino acids) with 5 distinct domains that exert different functions that inevitably lead to apoptosis
and cell death. NS1 activates cell death through two different pathways, apoptosis/lysosomal-like programed cell death and
necrosis/cytolysis.[26]

Action [ edit ]

NS1 is considered a regulatory protein due to its activity in transcription, translation, and protein-protein interactions, which allows the
parvovirus to replicate unhindered. However, scientists are primarily interested in utilizing its cytolytic activity since this has been proven
to be active in cancerous cells. The first way NS1 propagates cell death through cytolysis is by interrupting the cell cycle at the S/G2
junction, causing a stress response in the cell. Specifically, NS1 interacts with many molecules and compounds important in the transition
and inhibits their activity. When NS1 expression reaches a certain threshold, the triggered stress response finally causes caspase 3/9-

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 mediated programmed cell death.[26] Another way that NS1 causes cytolysis is through degradation of the cytoskeleton of the cell. NS1
specifically targets and degrades the microfilament tropomyosin using casein kinase II, actin filaments through activation of actin-severing
protein gelsolin, and vimentin through an unknown mechanism.[27][28][29] The last NS1-mediated mechanism of cytolysis involves the
depolarization of the mitochondria. This results in the release of many reactive oxygen species, causing DNA damage. When DNA is
damaged, a DNA damage response occurs, which in this case results in cell death.[30]

ORCTL3 [ edit ]

History [ edit ]

Organic Cation Transporter Like-3 (ORCTL3) was first discovered as a result of a large-scale DNA sequencing project in search of genes
with a tumor-specific apoptosis activity.[31] The name ORCTL3 was decided upon because of its structural homology to proteins
belonging to the family of organic cation transporters.[32] However, the name is a misnomer as after examining the properties of ORCTL3,
it was revealed that ORCTL3 is a transporter for urate. The ORCTL3 gene spans around 12 kb of genomic DNA and consists of ten
exons. It was shown that the 2.4 kb transcript of this gene is universally expressed in all human tissues. Additionally, ORCTL3
transfection into numerous tumorigenic cells induced apoptosis, while normal and primary cells remained healthy.[33]

Action [ edit ]

ORCTL3 is a 90 kDa protein composed of 351 amino acids.[34][35] It is suggested that the protein spans the cell membrane several times,
based on computational methods.[36] Overexpressed ORCTL3 is localized to the endoplasmic reticulum (ER), Golgi and the plasma
membrane but not to mitochondria.[33] ORCTL3 was identified as the first high-affinity nicotinate exchanger in kidneys and intestine.
Nicotinate is an essential vitamin (Vitamin B3) that is involved in NAD+ synthesis, which in turn is important for energetic processes,
signal transduction pathways, and the activation of the NAD+ -dependent histone deacetylase SIRT1. ORCTL3 has been shown to be
activated for apoptosis induction in renal cells in vitro, in vivo and ex vivo. For its apoptosis effect ORCTL3 targets stearoyl-CoA
desaturase (SCD), an enzyme that introduces a double bond in the fatty acid stearic acid.[37] The fact that SCD is commonly
overexpressed in cancer and oncogene transformed cells might explain the tumor-specificity of ORCTL3 to some extent, however, the
existence of other additional targets of ORCTL3 cannot formally be ruled out.

Par-4 [ edit ]

History [ edit ]

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 Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein with a pro-apoptotic function. Par-4 was first discovered in rat
prostate cancer cells as part of an effort determined in discovering genes that were induced in response to increased Ca2+ in cells,
although it is now known to be ubiquitously expressed in a wide variety of tissues across many different species.[38] The Par-4 gene is
located on the minus strand of chromosome 12q21.2, spanning 99.06 kb of DNA and containing seven exons and six introns. Par-4 is
known to be downregulated in certain terminally differentiated cells such as neurons, specific retinal cells, and smooth muscle cells as
well as in certain cancer cells such as renal cancers, neuroblastoma, and leukemia.[39][40] Par-4 has also been shown to be generally
higher in dying cells, consistent with its pro-apoptotic functions.

Action [ edit ]

Par-4 is a 38 kDa multi-domain protein composed of about 340 amino acids. Conserved domains among human, mouse, and rat
homologs include the leucine zipper (LZ) domain at the C-terminal region, two nuclear localization sequences, NLS1 and NLS2, in the N-
terminal region, and a nuclear export sequence within the LZ domain.[41] Although Par-4 mutations are rare, it was identified that an A to
T point mutation affecting residue 189 localized in exon 3 causes premature termination of Par-4 in human endometrial carcinoma.[42]
Knockout of Par-4 in mice leads to the development of spontaneous tumors in various tissues revealed by increased proliferative
response of peripheral T cells, inhibition of apoptosis, increased NF-κB activity, and decreased JNK activity.[43] Par-4 overexpression is
sufficient to induce apoptosis in most cancer cells in the absence of a second apoptotic signal, but does not induce apoptosis in normal or
immortalized cells.[41][44][45]

The anticancer function of Par-4 is achieved by two distinct means: activating the molecular components of the cell-death machinery and
inhibiting pro-survival factors. One essential apoptotic function of Par-4 is inhibiting the NF-κB pathway, which is a key contributing factor
in many tumors and prevents cell death by activating the expression of pro-survival genes. Par-4 also assists in PCD by enabling the
trafficking of specific ligands such and cell surface death receptors, such as FasL and Fas, respectively, to the plasma membrane thus
activating the extrinsic death pathway. Overexpression of Par-4 selectively induces apoptosis in cancer cells, attributed to the selective
activation via phosphorylation of the T155 residue by protein kinase A (PKA).[46] It has been shown that two events are required for Par-4
activation: nuclear entry and phosphorylation by PKA.

TRAIL [ edit ]

History [ edit ]

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (Figure 5) is a member of the tumor necrosis factor (TNF) family that
also includes Fas ligands, TNFα, and TL1A. It was discovered in 1995 by Wiley et al. and then further characterized in 1996 by Pitti et al.

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 The former study discovered that TRAIL is localized to surfaces of cells in most
human tissues, excluding the brain, liver, and testes,[47] while the latter study was
able to elicit that the protein is a type II membrane protein that can also be cleaved
into a soluble form.[48]

Action [ edit ]

The intrigue surrounding TRAIL is all due to this protein's ability both in vivo and in
vitro to specifically target tumor cells for apoptosis while leaving healthy cells intact.
This activity proceeds by both the intrinsic and extrinsic pathway. First, the
homotrimer of TRAIL binds three molecules of either TRAIL-receptor 1 or 2, which
are transmembrane proteins that contain a cytoplasmic death domain. Once TRAIL
is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming Figure 5: Crystal Structure of Human TRAIL.

death-inducing signaling complex (DISC) that proceeds through two different

mechanisms depending on the cell type. In one cell type, DISC can directly activate the effector caspase leading to apoptosis, while in the
other the complex activates a bcl-2-mediated pathway in a similar fashion as HAMLET that results in the release of cytochrome c from
the mitochondria, which then causes the activation of effector caspase. The latter mechanism is the focus of many oncogenic therapies
because p53, the tumor suppressor gene, activates the same pathway. Since cancer is commonly caused by the inactivation of p53,
TRAIL could mediate this effect by still activating the apoptotic pathway.[49]

TP53 [ edit ]

History [ edit ]

TP-53 (Figure 6) is a gene that encodes for the protein p53; this protein is a tumor suppressor. p53 was discovered in 1979 stemming
from a study involving cancer immunology and the role of viruses in some cancers. The protein was so named because it was measured
to have a weight of 53 kDa. This study was conducted by David Philip Lane and technician Alan K. Roberts, in Lionel V. Crawford's lab in
London. It was seen in this study that p53 could bind to viral tumor antigens. This information was corroborated during the same year
when a separate study found that p53 had immunoreactivity with serum from tumors containing antibodies. This later study was run by
Daniel I. H. Linzer and Arnold J. Levine out of Princeton University. Further papers came out around the same time all mentioning the
discovery of a tumor suppressing protein. While p53 was first officially identified in 1979, many labs in previous years had come across
the same protein, without knowing what it was. In the mid-1970s, a scientist by the name of Peter Tegtmeyer happened upon a protein

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 with an approximate size of 50 kDa. However, because he was focusing his
studies on SV40, a tumor-causing virus affecting monkeys and humans, he did
not pay much attention to this protein.[50]

Action [ edit ]

The p53 protein is a tumor-suppressing transcription factor (TF), which can

recognize when there is an alteration in a cell's DNA caused by factors
including chemical toxins, radiation, ultraviolet (UV) rays, and other damaging
agents.[51] Crucially, p53 plays a role in determining whether the damaged
genetic material in the cell can be repaired, or if the cell should be destroyed
through apoptosis.[52][53] The individual topologically associating domains
(TADs) target different genes and unique effector pathways. It has been
observed that inactivating both of the TADs detrimentally affects the ability of
p53 to suppress tumor growth and interact with target genes. When only one Figure 6: Structure of TP53 bound to DNA.

TAD is inactivated, p53 can still suppress specific tumors; however, it can no
longer successfully engage in transactivation. The C-terminal domain (CTD) is an intrinsically disordered domain (IDD), which can take
on different conformations depending on what it is binding with and is a location of many post-translational modifications, resulting in its
ability to regulate p53 function depending on what it is bound to and what modifications are linked with the CTD. This domain also aids in
the binding of the central DNA-binding domain (DBD) to specific DNA sequences; the CTD is a positive regulator of DNA binding and
stabilizes the interaction of the DNA with the DBD.[51] p53 is unique as a transcription factor in that it can recognize and bind response
elements (RE) in many different environments and doesn't need other transcription factors to cooperatively bind with it like many other
TFs.[51]

Mutations in the p53 pathway have been observed in almost all cancer types including breast cancer, bladder cancer, lung cancer,
ovarian cancer, cholangiocarcinoma, head and neck squamous cell carcinoma, melanoma, wilms tumor, and other cancers often due to a
single point mutation in p53.[52][53] Li-Fraumeni Syndrome is a condition linked to inherited mutations, at least 140 mutations, in the TP-53
gene. This condition largely increases the risk of developing cancers like breast cancer, bone cancer, and soft tissue sarcomas.
Specifically, this impacts children and young adults. A majority of these mutations in the TP-53 gene are single amino acid changes, but
other mutations cause a small portion of the DNA to be absent. This leads to a faulty p53 protein that fails to recognize DNA damage in
cells, control cell growth, and initiate apoptosis in cells with damaged DNA. Consequently, cells containing erroneous DNA can
uncontrollably divide.[52]

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 Common misconceptions [ edit ]

Often, genes are confused with the proteins in which they code for (Figure 7). Genes are composed of nucleotides, while proteins are
composed of amino acids. The genes serve as codes and blueprints to create either proteins of interest, or various non-coding
ribonucleic acids (ncRNAs), which exhibit various effects, such as working to prevent cancer within cells.

Figure 7: Central Dogma schematic depicting the protein product via the
transcription and translation of a gene.

See also [ edit ]

Oncogene
Gene therapy for cancer
Tumour suppressor gene
Cell Cycle
Cell Cycle Checkpoints
Genes
Proteins

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 Apoptosis
HAMLET
Par-4

References [ edit ]

1. ^ Futreal, P. Andrew (2009). "A census of human cancer genes" . 7. ^ a b c Jamadi, Robab (2020). "Anticancer Activity of Brevinin-2R
Nature Reviews Cancer. 4 (3): 177–183. doi:10.1038/nrc1299 . Peptide and its Two Analogues Against Myelogenous Leukemia
PMC 2665285 . PMID 14993899 . Cell Line as Natural Treatments: An In Vitro Study". International
2. ^ ab Olugbami, Jeremiah. "A comparative assessment of Journal of Peptide Research and Therapeutics. 26 (2): 1013–1020.
antiproliferative properties of resveratrol and ethanol leaf extract of doi:10.1007/s10989-019-09903-6 . S2CID 199407384 .
Anogeissus leiocarpus (DC) Guill and Perr against HepG2 8. ^ abc Zohrab, Fatemeh. "Biological Properties, Current
hepatocarcinoma cells". BMC Complementary and Alternative Applications and Potential Therapeutic Applications of Brevinin
Medicine. 17: 1–11. Peptide Superfamily". Nature Public Health Emergency Collection.
3. ^ Grimm, Stefan; Noteborn, Mathieu (2010-02-01). "Anticancer 25: 39–48.
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