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I.8.

Signaltransduction
Cell Cycle
Cell Division
Cell death
Cancer
Please outline the importance, participants and types of the
signaltransduction in a multicellular organism!

Please give a definition for the cell cycle and outline its phases!

Please define and outline main phases of the mitosis!

Please define meiosis with its importance and outline main


phases of it!

Please describe possible forms of the cell death and outline


the main differences between them!

Please describe main characteristisc of a malignant tumor


cell/tissue!
SIGNAL TRANSDUCTION

how do our cells talk to each


other?
General principles of cell
communication
Why? When it all started?

Individual cell survival – 3.5billion yrs ago


The multicellular organism’s survival – 1.5 billion yrs ago

2 billion yrs difference! What for?

The switch between, the


Individual benefit – for the benefit of the organism as a
whole
KEY: communication
Budding yeast cells
responding to mating factor

(A) The cells are normally


spherical.
(B) In response to mating
factor secreted by
neighboring yeast cells,
they put out a protrusion
toward the source of the
factor in preparation for
mating. (Courtesy of
Michael Snyder.)
From: General Principles of
Cell Communication
In a multicellular organism things are muh
more complicated
Q:Please outline the importance,
participants and types of the
signaltransduction in a multicellular
organism!
Signaltransduction is the way how cells communicate with each other in a
multicellular organism. Its importance lies in coordination the work
between the billions of cells they have, as jobs are devided between the
organs /tissues / different cell types. The overall goal to maintain the
homeostasis and to direct the development.
Participants: study it on the next slide: signalling cell, ligands, target
cells (with specificreceptor!)
Types: you can group sd processes in different ways by e.g. receptor
types (cell surface, IC – see on slide 9th// ion channel, G-protein linked,
enzyme linked – see on slide 11th) or by distance between the cells that
communicate: juxtacrin, paracrin, endocrin, neurocrin (see on slide 14th!)
Cell communication: signaltransduction
Signalling Ligand Target cell
cell
Aminoacid, peptide
Nukleotide
Sterol, fatty acid derivatives,
gases (NO, CO)
…practicly anything… that can be recognised by a
RECEPTOR of the target cell

Ligands are released by


exocytosis/diffusion or (ligand=
are remaining tightly
chemical signal
bound to the signaling
cell's surface
=signal molecule)
The binding of extracellular signal molecules to either cell-
surface receptors or intracellular receptors

Figure 15-3. The binding


A simple intracellular
signaling pathway
activated by an
extracellular signal
molecule
Insulin binding to the insulin receptor induces a signal transduction
cascade which allows the glucose transporter (GLUT4) to transport
glucose into the cell.
In contrast: acting of a
steroid hormone, that
can enter the cell, and
the nucleus itself
Extracellular Signal Molecules Can Act Over Either
Short or Long Distances
Autocrine Signaling Can Coordinate
Decisions by Groups of Identical Cells

Figure 1
signaling. A group of identical cells produces a higher concentration
does a single cell. When this signal binds back to a receptor on the sa
encourages the cells to respond coordinately as a group.
Each Cell Is Programmed to Respond to Specific
Figure 15-7. Signaling via gap junctions. Cells connec
Combinations of Extracellular Signal
junctions share small molecules, including Molecules
small intracellular signaling molecules,
therefore respond to extracellular signals in a coordinated

way. Figure 15-8. An anim


dependence on multiple extracellular signals. Each cell type displays a set of re
enables it to respond to a corresponding set of signal molecules produced by other
Q: Please give a definition for the cell cycle and outline its
phases!
The Cell Cycle definition as follows:
The cell cycle is an ordered set of events, culminating in cell growth
and division into two daughter cells. Non-dividing cells not
considered to be in the cell cycle

Phases (2 main and many other sunphases as follows):


Interphase: G1+S+G2. The G1 stage stands for "GAP 1„:
preparation for the DNA replication. The S stage stands for
"Synthesis„: the semiconservative DNA replication itself. This is the
stage when DNA replication occurs. The G2 stage stands for "GAP
2„: preparation for cell division.
Mitosis (cell division): see detailed phases of the mitosis later
(You can write them here as well, like prophase, metaphase…etc)
Cell division

Interhase
During S Phase of the Interhase DNA is
Replicated
The control of
the cell cycle
Figure 15-7. Signaling via gap junctions. Cells c
junctions share small molecules, including small intracellular signaling mole
Multiple signals – cell’s decision
therefore respond to extracellular signals in a coordinated

way. Figure 15-8. A


Types of Cell Division
Q: Please define and outline main phases of the mitosis!

Definition:
Mitosis is common form of cell division to all eukaryotes; during this process, a
parent cell splits into two genetically identical daughter cells, each of which
contains the same number of chromosomes as the parent cell.

Phases:
For the simpliest answer pls study the next slide!
e.g.
Prophase: chr.s become visible, spindle fibers formation starts, nuclear envelope
breaks down
Metaphase: chr.s at the metaphase plate, spindle fibers attached to them
Etc. For all phases
Kinetochore and
Mitotic Spindle:

During prometaphase,
mitotic spindle
microtubules from
opposite poles attach
to each sister
chromatid at the
kinetochore. In
anaphase, the
connection between
the sister chromatids
breaks down and the
microtubules pull the
chromosomes toward
opposite poles.
Mitosis Stage 3: Metaphase: Mitotic spindle
The main differences between mitosis and meiosis
What is „crossing over” during meiosis and its
importance ?
Q: Please define meiosis with its importance and outline main phases of it!

Definition:
meiosis, also called gametogenesis, is the process of reducing cells to half their
chromosomal number: for humans this means cutting their chromosal number
down from 46 to 23. A cell which has had its chromosome number reduced to half
is called a "haploid" cell. The purpose of meiosis is to prepare a cell that will be
capable of sexual reproduction: able to combine with another haploid cell to
make a new organism.
Phases:
Meiosis is split into two separate parts, called meiosis I and meiosis II.
Meiosis I : consist of the same phases like in mitosis (pro-, meta-, ana- and
telophases), just there are important differences that has to be mentioned:
instead of lining up in single file, homologous chromosomes line up two-by-two
(process starts in prophase, finished in metaphase): crossing over may occur and
homologous chromosomes will separate during the anaphase of meiosis I
(compare this to the anaphase of mitosis, where chromatids separate!).
Meiosis II applies the process of mitosis to the two cells created by meiosis I.
Since the chromosomes already exist in the bivalent form(2 chromatids, they
consists of), interphase is skipped. The result is four cells, called gametes, each
with two monovalent chromosomes.
Human gametogenesis
Figure 15-7. Signaling via gap junctions. Cells c
junctions share small molecules, including small intracellular signaling mole
Multiple signals or lack of them – cell’s decision
therefore respond to extracellular signals in a coordinated

way. Figure 15-8. A


Q: Please describe possible forms of the cell
death and outline the main differences between
them!
Apoptosis:
Programmed cell death. All the processes of it are directed by the cell
itself. (triggers and detailed processes see on slide 37th and 38th). This is
a necessary process during development or replacement of scenescent
(„aged”) cells.

Necrosis:
Cell death caused by external factors like physical injury, toxins or
radiation. This is a pathological process acompained with lysis of the
plasma membran.

Autophagy:
„Self-eating” of the cells with lisosomes. This process may lead not only to
death of it, but gives possibility for self renewal as well by clearing away
run-down organelles.

Mitotic catastrophe:
Sudden cell death during mitosis, if checkpoints find problems.
Importance: to avoid chromosomal anormalities. It is a kind of „emergency
break”.
+ mitotic catastrophe
CELL DEATH

NECROSIS APOPTOSIS
pathological physiological
necros = dead body Fall of the leaves from the
trees in autumn
(apo = apart, ptosis =
fallen)
NECROSIS

• A pathological response to cellular injury

• Chromatin clumping

• Mitochondria swelling and rupture

• Plasma membrane lyses

• Cell contents spill out

• General inflammatory response is triggered


Apoptosis (programmed cell death)

External triggers Internal triggers

Lack of growth factors DNA damage

Apoptosis inducing signals


Mitochondrial damage
planned apoptosis during
intrauterine divelopment
Incorrectly folded proteins
, „death ligands” presented by accumulating in the ER
„killer cells” of the immune
system

APOPTOSIS
Initiator caspases

effector caspases human frog

cytoskeleton, DNA, protein degradation


Apoptosis (programmed cell death)

A, lamins and actin filaments (cytoskeleton)


degraded  shrinking

B, chromatin degrading, nucleus condensing

C, D: „packaging”, apoptotic bodies are released

E, macrophages clean up the remains


via phagocytosis
Autophagic Cell Death/Survival
Mitotic Catastrophe
Q: Please describe main characteristisc of a malignant
tumor cell/tissue!
SHORT ANSWER:
•gives metastasis (invasive)
•can grow without restrictions
• increased motility
•drug resistant
•Independent from growth factors
apoptosis resistant

1. DETAILED EXPLANATION TO STUDY NOT NECESSARY EXPLAIN DETAILED IN THE TEST


2. Self-sufficiency in growth signals: Cancer cells produce their own growth signals and proliferate without
environmental cues.

3. Evading apoptosis: Tumor cells avoid apoptosis and expand in number.

4. Sustained angiogenesis: Cancer cells induce and sustain blood vessel growth.

5. Limitless potential for replication: The DNA of tumor cells can replicate an infinite number of times.

6. Tissue invasion and metastasis: Tumor masses spawn pioneer cells that colonize sites where nutrients
and space are not limiting

7. Insensitivity to antigrowth signals: Cancer cells evade antigrowth signals in order to proliferate. (they may
develop drug resistance as well)
Cancer—Uninhibited Cell Division

• Cause: DNA Damage or Change


– Changes in one or more of the genes that control
the production of enzymes involved in cell cycle.

SOURCES

1. Exposure to radiation 5. Nutrition and diet


2. Exposure to toxins 6. Tobacco use
3. Hormonal abnormalities 7. Viral infection
4. Inherited abnormalities
H.pylori is
actually a
bacterium,
and also…*
benign malignant

•non invasive
•can’t spread to other organs
•If operable, it won’t return after
surgical removal
•Still can cause complications or
death if it grows in the wrong place
•can trasform into a malignant
tumor over the years
•gives metastasis (invasive)
•can grow without restrictions
• increased motility
•drug resistant
•Independent from growth factors
apoptosis resistant
carcinogen  tumor initiation (causes DNA damage, increases the risk of mutations)
promotes cell proliferation  tumor promotion

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