Exam #4 Cell Cycle Flashcards
Four Stages of the Cell Cycle
- M= Mitosis, when the cell dividies
- G1= Growth period the precedes DNA synthesis
- S= DNA synthesis/replication to form two sister chromatids attached at centromere
- G2= Second period of growth the precedes cell division
Stages of the Cell Cycle that Comprise Interphase
Interphase is the time between cell divisions
- G1
- S
- G2
Cyclin-CDK Complexes of M-Phase
- Cyclin A/CDK1
- Cyclin B/CDK1
Cyclin-CDK Complexes of Mid G1 Phase
- Cyclin D/CDK 4
- Cyclin D/CDK6
Cyclin-CDK Complexes of Late G1 Phase
Cyclin E/CDK2
Cyclin-CDK Complexes of S Phase
Cyclin A/CDK2
Contact Inhibition
- Cell - Cell contact usually inhibits cell division
- This “contact inhibition” is lost in cancer
- Cell - ECM contact does the opposite
Growth Factors
- Molecules that stimulate cell growth/division
- PDGF, EGF, nerve growth factor, and insulin-like growth factor 1 are examples
Growth Factor Receptors
- Intrinsic Tyrosine Kinase
- Ligand (growth factor) binds to receptor & triggers receptor dimerization & autophosphorylation or tyrosine residues within the receptor
- Phosphotyrosine residues are docking sites for signaling molecules
GRB2, Sos, & Ras
- GRB2= adapter protein that binds phosphotyrosine residues
- Sos= Guanine Nucleotide Exchange Factor, activates Ras
- Ras= G-Protein that is activated by SOS
Raf, MAP kinase kinase, MAP kinase
- Ras activates the protein kinase Raf
- Raf phosphorylates & activates MAP Kinase Kinase (MEK)
- MAP Kinase Kinase phosphorylates & activates MAP Kinase
- MAP Kinase translocated to the nucleus and stimulates c-Fos transcription
- End result= progression through the restriction point
Early Response Genes
- Growth factor added to cell in G0 results in a burst of transcription
- Genes transcribed in this initial phase are “early response genes”
- Includes c-Fos, c-Jun, and c-Myc
Delayed Response Genes
- Genes transcribed in response to c-Fos
- Encode more transcription factors & Mid/Late G1 Clycin-CDKs
Why is phosphorylation of Rb important?
It stimulates progression through the restriction point and renders the cell cycle growth factor independent
What kinases phosphorylate Rb?
- CDK 4 & CDK 6 (Cyclin D regulated) initially
- CDK 2 (Cyclin E regulated) secondarily
How is cyclin A-CDK2 inhibited?
p27-KIP1