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Oncogenes
Genes that can cause cancer when mutated or overexpressed.
Evidence for oncogenes
Harder to overexpress, easy to underexpress, and easy to silence, often using RASGAP.
Inactivating both copies of oncogenes
Unlikely to occur.
SNPs (Single Nucleotide Polymorphisms)
The most common type of genetic variation, affecting cancer susceptibility, progression, and treatment outcomes.
Tumor suppressor genes
Genes that help prevent uncontrolled cell growth and are influenced by SNPs.
RB (Retinoblastoma protein)
Regulates the transition from G1 phase to S phase in the cell cycle.
CDK (Cyclin-Dependent Kinase)
Serine and threonine kinase that plays a key role in regulating the cell cycle.
Cyclin
Regulatory protein that, when bound to CDK, activates its function.
Lamins
Proteins responsible for the disassembly of the nuclear envelope.
Mechanisms of CDK regulation
Include abundance of cyclins, binding to CKIs, and CDK phosphorylation.
Cyclin box
Region that binds to CDK and is crucial for its activation.
PEST sequence
A sequence rich in proline, essential for cyclin-dependent regulation.
Destruction box
Region responsible for cyclin degradation.
Cytoplasmic retention sequence
Sequence that retains cyclin in the cytoplasm.
Mono-Ub (Monoubiquitination)
Regulates protein activity.
Poly-Ub (Polyubiquitination)
Marks cyclins for degradation.
E1 enzyme
Activates and regulates proteins by attaching ubiquitin.
E2 enzyme
Facilitates the conjugation of ubiquitin to the substrate.
E3 enzyme
Functions as a specificity factor in ubiquitin ligation.
SCF complex
A complex made up of SKP, Cullin, and f-box components.
Anaphase promoting complex (APC)
Promotes cyclin degradation and cell cycle progression.
K48 ubiquitination
Targets proteins for destruction by the proteasome.
K63 ubiquitination
Acts as an organizer in cellular processes.
CAK (CDK-Activating Kinase)
Phosphorylates Thr160 to activate CDK.
Thr160 phosphorylation
Opens the activation loop and stabilizes the active conformation of CDK.
Wee1
A kinase that inactivates CDK by adding a phosphate, blocking its active site.
CDC25
A phosphatase that activates CDKs by removing inhibitory phosphates.
Positive feedback loop
Occurs when mCDK increases as cyclin increases.
INK4
A CDK inhibitor that blocks cyclin D activity.
CIP/KIP
CDK inhibitors that block the active site of CDKs.
KIP1
Inhibitor that obstructs the ATP binding site of CDK.
CIP/KIP interaction with cyclins
CIP/KIP proteins remain bound to cyclins.
E2F
Protein that regulates the cell cycle and is crucial for DNA synthesis and S-phase entry.
E2F binding to pocket proteins
Phosphorylates Ser567 and retinoblastoma, influencing cell cycle regulation.
Function of E2F
Regulates the cell cycle and controls genes necessary for DNA synthesis.
NLS (Nuclear Localization Signal)
Helps localize E2F to the nucleus and is important for transcription.
Cyclin A in the S phase
Facilitates transitions during DNA synthesis.
Cyclin A in the G2 phase
Helps activate and stabilize proteins for mitosis.
MCDK (M-phase Cyclin-Dependent Kinase)
Promotes the activity of APC/C during mitosis.