5 Flashcards
What are Immediate Early Genes
Immediate Early Genes (IEGs) are a group of genes that are rapidly and activated in response to external stimuli (such as growth factors, stress signals, or cellular signals), without the need for protein synthesis
Example:
c-jun
c-fos
c-myc
what are homologous to retroviral oncogenes ?
v-myc
v-fos
v-jun
What forms the AP-1 complex ?
c-jun and c-fos (via dimerization)
**AP-1 binds to specific response elements in many genes
Cyclohexamine and c-fos/c-jun
Cycloheximide blocks new protein synthesis
Although c-Fos and c-Jun are rapidly synthesized as IEG products, cycloheximide can prevent their function by inhibiting the synthesis of subsequent proteins that support their stable activity or further signalling events.
What is MMP-1 and why does its transcription (and translation) increase?
MMP-1 is an enzyme that breaks down the extracellular matrix (ECM)
transcription and translation increase in response to inflammatory signals, tissue injury, growth factors, cancer progression, and mechanical stress, all of which require ECM remodeling
what does AP-1 induce?
It is involved in regulating the expression of various genes in response to a variety of stimuli such as growth factors, stress signals, cytokines, and oxidative stress.
What is a key regulator of Mitosis (cell cycle)
Cyclin D1
(entry into G1 Phase)
Name one homodimer and one heterodimer
Hetero: AP-1 comples (fos/jun)
Homod: HER2
What do Cyclin Dependant Kinases do (CDKS) and what are the ones we know of?
CDKs regulate cell cycle progression
- CDK4 –> cyclin D1
- CDK2 –> Cyclin E1
what domains are in most/all enzymes ?
- catalytic domain (active site)
- Binding domain (substrate attachment and regulation)
what are CKI’s and what are the ones we know of?
CKIs are Cyclin-Dependent Kinase Inhibitors, like p16, p21, and p27.
These are proteins that regulate the cell cycle by inhibiting cyclin-dependent kinases (CDKs)
Key Points in Retinoblastoma Signaling?
- Rb is a critical negative regulator of the G1/S transition in the cell cycle.
- regulated by phosphorylation, through cyclin D/CDK4/6.
- Loss of Rb function leads to unregulated cell cycle progression/cancers
- Rb interacts with E2F transcription factors, and its phosphorylation controls the activation of genes required for DNA synthesis and cell division.
What makes Rb no longer able to bind to E2F?
Hyperphosphorylation of Rb
What happens when Rb is no longer bound to E2F?
E2F is free to Transcribe genes for S Phase (cell cycle progression)
When you see ”v” or viral in front of a gene it is ?
Means it is oncogenic
- v-src
- v-jun
- v-fos ….
What are the DNA Repair genes?
BRCA1/2
- they are tumor supressors for Breast cancer 1/2
Is Rb an POG or a TS?
Tumor supressor
AKT aka?
PKB
PTEN does what ?
converts PIP3 to PIP2
AKT promotes what?
Promotes Cell survival and proliferation
- inhibits APop
- inhibits p27 activity
How does PTEN Regulate Signaling?
PTEN opposes PI3K signaling by converting PIP3 → PIP2, preventing Akt activation and ultimately inhibiting cell growth, survival, and tumor progression.
Is PI3K a TS or a POG?
Proto-oncogene
subunits and their function in PI3K
- p85 subunit is the inhibitory/regulator factor of - PI3K. It has two SH2 domains
- p110 is the catalytic domain
