Cell Cycle Flashcards
name the different phases of the cell cycle
G1 or preparatory phase, longest phase
S phase, where DNA replication happens
G2 phase, where the cell is preparing for mitosis, checking for the right order
M phase - mitosis
Cytokinesis, cells split into two
endoreduplication
cells with more than 2n copies of DNA
cells go through cell cycle stopping before mitosis
replication without splitting over and over again
interphase
the time when the cell grows and replicates its DNA, divded into G1, S, and G2
cyclin-dependent kinases (Cdks)
family of 11 related protein kinases, crucial for cell cycle progression and other activities
binds to cyclins, and Cdk-cyclins only have partial kinase activity
phosphorylation of specific amino acids on the Cdks can either activate or inhibit the kinase
cyclins
bind to Cdks, at least 16 differeny cyclins, have varying levels during the cell cycle to dictate what happens at different points in time during the cell cycle
four mechanisms that regulate Cdk activity
- Association with cyclins
- activating phosphorylation of threonine around position 160
- inhibitory phosphrylation of threonine 14 and 15
- Association with Cdk inhibitors (CKIs)
CKI
cyclin-dependnt kinase inhibitor, along with inhibitor of Cdk4 (INK4 families bind to and activate the Cdk-cyclin complexes
some members of the CKI family also can act as positive cofactors for Cdk-cyclin assembly and activation
Describe the four classes of cyclins that affect Cdk activity throughout the cell cycle.
Cyclin D synthesis beings in G1 and stays relatively constant until it is degraded and disappears through mitosis
Cyclin E is the G1/S cyclin, rises at the end of G1 and rapidly decreases at the beginning of S phase
Cyclin A is important for S phase and transition through G2
Cyclin B increases throughout G2 and then drops during mitosis after it peaks
cyclical proteolysis of CKIs
SCF phosphorylates CKI and makes it a target for E1 and E2 ubiquitin ligase, which targets the CKI for degradation
cyclical proteolysis of cyclins
done by APC after an activating subunit Cdc 20
ubiquitinylates cyclin/Cdk complex
APC = Anaphase promoting complex
M-Cdk activates APC, negative feedback loop
three major cellc ycle checkpoints
G1/S, G2/M, and M/cytokinesis
cell growth signals
GSK3beta and Ras
GSK3beta inhibits formation of Cyclin D1/Cdk4, Cyclin D1/Cdk6, and Cyclin E/Cdk2
Ras promotes Cyclin D1/Cdk4 and Cyclin D1/Cdk6
TGFbeta
binds to a surface receptor serine-threonine kinase
signaling cascade promotes Smad3 and Smad4, which indirectly inhibits cdc25A and subsequently Cyclin D1/CDK4
Smad3/4 also indirectly inhibits p15 thorugh 19
differentiation signals
p15 through 19, which inhibit Cyclin D1/Dck4 formation
cell-cell-ECM contacts
activate GSK3beta and RhoA
GSK3beta inhibits beta-catenin/TCF, which indirectly activates Cyclin D1/Cdk6/4
RhoA indirectly inhibitis p21 and p27, which inhibit Cyclin D1/Cdk6/4 as well as Cyclin E/Cdk2