Group 7

Regulation of gene
expression at protein level
Dr. Nguyen Hoang Chuong
 Group members
Full name Student ID
Phạm Minh Anh 22187008
Mai Xuân Cảnh 22187011
Phạm Trung Đức 22187019
Nguyễn Trần Quang Huy 22187044
Lê Minh Trí 22187150
 Table of contents

01 02
Regulation of Regulation at
gene expression translational level

03 04
Regulation at
References
post-translational level
01
Regulation of gene
expression
 Regulation of gene expression

• A cell must have gene regulation mechanisms

• Regulation of gene expression at protein level is related to the
regulation mechanisms at the translational and post-translational levels
• Regulation at translational level refers to the controling of the
translation process
• Regulation at post-translational level often refers to post-translational
modifications (PTMs)
 02
Regulation at
translational level
 Regulation at translational level
• Is important in response to internal and external signals.
• Occurs at several stages (initiation, elongation, and termination)
• Is more often seen in eukaryotic cells.
 Regulation at translational level
• Most common target of translational control: translation initiation (by
controling eIFs).
• A key event in initiation: the formation of the 43S pre-initiation complex
• The binding of Met-tRNAi to the rRNA is dependent on the activity of
the protein complexes eIF2 and eIF2B.
• The binding of 43S pre-initiation complex to mRNA is regulated by other
translation initiation factors (such as eIF4F)
 2.1. Translational functions of the eIF4F complex
and inhibition by the 4E-BPs

• eIF4F is composed of eIF4E, eIF4A

and eIF4G
• eIF4G interacts with the two protein
kinases that phosphorylate eIF4E, the
MAPK-integrating protein kinases 1
and 2 (MNK1 and MNK2)
2.1. Translational functions of the eIF4F complex
and inhibition by the 4E-BPs

• In the presence of apoptotic signals,

eIF4E interacts with 4E-BP1 and 4E-BP2
(eIF4E-binding proteins 1 and 2)
• 4E-BP1 and 4E-BP2 are
hypophosphorylated (in stresses &
apoptosis) and disrupt the eIF4E-eIF4G
complex.
2.2. Regulation of eIF2 and eIF2B due to stresses
2.2. Regulation of eIF2 and eIF2B due to stresses

Four different protein kinases can phosphorylate eIF2α:

 HRI (heme-regulated inhibitor kinase)
 PKR (protein kinase RNA-activated) – activated by generation of dsRNA
in virus infection
 PERK (RNA-dependent protein kinase-like endoplasmic reticulum
kinase) – activated upon ER stress.
 GCN2 (general control nonrepressed 2) – activated upon nutrient
deprivation and other stresses.
2.2. Regulation of eIF2 and eIF2B due to stresses

GSK-3β (glycogen synthase

kinase-3β) is activated by
amino acid and growth
factor deprivation.
03
Regulation at
post-translational level
 Regulation at post-translational level
• Mostly due to post-translational modifications (PTMs)
• PTMs refer to amino acid side chain modifications in some proteins
after their biosynthesis.
• Have significant impacts on structure and function of proteins.
• PTMs occur in slightly diffenrent manners in both prokaryotic (less
diverse) and eukaryotic cells (more diverse).
• Disruption in PTMs can lead to the dysfunction of vital biological
processes resulting in various diseases.
 Phosphorylation

SUMOylation Glycosylation
5
well-studied
PTMs

Ubiquitylation Methylation
3.1. Phosphorylation
• This PTM includes attachment of a phosphate group from an NTP
molecule to the protein residues by kinase enzymes.
• This mechanism controls the activities of many enzymes, membrane
channels and many other proteins.
• Dephosphorylation: a removal of a phosphate group and is catalyzed
by phosphatases. This modification can rapidly alter the activities of
proteins via two principal ways: by allostery or by binding to
interaction domains.
• Phosphorylation takes part in many significant cellular processes such
as replication, transcription, apoptosis, etc.
3.2. Glycosylation

• Glycosylation is a reversible PTM that occurs in eukaryotic and

prokaryotic membranes and secreted proteins.
• In this modification, oligosaccharide chains are linked to specific
residues by covalent bond under the activity of a glycosyltransferase
enzyme.
• Glycosylation has a great role in many important biological processes
such as cell adhesion, cell–cell recognition, signal transduction,
secretion of protein, etc.
3.3. Methylation

• Methylation is a reversible PTM, which mainly targets lysine and

arginine residues of the target proteins.
• One of the most important roles of methylation is in histone
modification.
• Methylation has been found to be involved in the regulation of many
biological processes ranging from transcriptional regulation to
epigenetic silencing via heterochromatin assembly.
3.4. Ubiquitylation
• It can occur on all 20 amino acids, but happens more frequently on lysine.
• This PTM can be removed by specialized proteases called deubiquitinases.
• Ubiquitylation is involved in various cell activities, such as degradation of
proteins, stem cell preservation, and differentiation by regulation of
pluripotency.

Degradation of polypeptide
chains via ubiquitin (Ub)-
proteasome pathway
 3.4. Ubiquitylation
Multi-poly-ubiquitylation

Multi-mono-ubiquitylation

Mono-ubiquitylation Poly-ubiquitylation

The ubiquitination cascade. The initial step involves the ATP-dep

endent... | Download Scientific Diagram (researchgate.net)
3.4. Ubiquitylation
Enzyme complex

1
2
3

Biological schematic diagrams of ubiquitination. (A) Schematic diagra

m... | Download Scientific Diagram (researchgate.net)
3.5. SUMOylation
3.5. SUMOylation

https://doi.org/10.1007/978-1-4419-7061-9_9
3.5. SUMOylation

DOI:10.3390/jof6010032
3.7. Examples of PTMs
 3.7.1. Subcellular localization of KH-type splicing
regulatory protein (KSRP) iin eukaryotic cells

KSRP structure

https://doi.org/10.3390/cells11091482
 3.7.1. Subcellular localization of KH-type splicing
regulatory protein (KSRP) iin eukaryotic cells

https://doi.org/10.3390/cells11091482
3.7.1. Subcellular localization of KH-type splicing
regulatory protein (KSRP) iin eukaryotic cells

Regulation of KSRP subcellular localization via

phosphorylation and SUMOylation
3.7.2. Regulation of PII signal transduction protein via
PTMs in prokaryotic cells

• PII proteins are essential for regulating nitrogen metabolism

• PII proteins orchestrate intricate signaling pathways to regulate nitrogen

metabolism efficiently.

• provides insights into optimizing nitrogen metabolism in various

organisms
3.7.2. Regulation of PII signal
transduction protein via
PTMs in prokaryotic cells

Regulation of PII activity via PTMs controling the

active status of GS
 04
References
 References
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504442/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040245/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475172/
4. https://www.researchgate.net/figure/Regulation-of-eIF2-activity-The-guanine-
nucleotide-exchange-activity-of-eIF2B-permits_fig1_235366723
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953056/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049097/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536343/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922605/
 References

9. Phosphorylation of the mRNA cap-binding protein eIF4E and cancer

10. https://www.thermofisher.com/vn/en/home/life-science/protein-biology/prot
ein-biology-learning-center/protein-biology-resource-library/pierce-protein-me
thods/overview-post-translational-modification.html
11. https://pressbooks-dev.oer.hawaii.edu/biology/chapter/eukaryotic-translation
al-and-post-translational-gene-regulation/
12. https://www.frontiersin.org/articles/10.3389/fmolb.2021.658852/full
13. Recent Insights and Novel Bioinformatics Tools to Understand the Role of
MicroRNAs Binding to 5 ' Untranslated Region
Thank you for listening!