BI203 Lecture 23: The Cell Cycle - Regulation of Cdk's (Slides 20 - 35) Flashcards
Proliferation of animal cells is also regulated by extracellular ___ ___ that control progression through the restriction point in late G1.
growth factors
Proliferation of animal cells is also regulated by extracellular growth factors that control progression through the restriction point in late ___.
G1
Presence of growth factors at the end of G1 leads to synthesis of ___ ___ via the Ras/Raf/MEK/ERK pathway.
cyclin D
Presence of growth factors at the end of G1 leads to synthesis of cyclin D via the ___/___/___/___ pathway.
Ras/Raf/MEK/ERK pathway
Cyclin D pairs with ___ to form the ___/___ ___ complex to push the cell through the restriction point at the end of G1.
Cdk4,6 Cdk4,6/cyclin D
Reminder: ___ ___ ___ can encode transcription factors and activate genes that promote cell proliferation, i.e. cyclin D.
immediate early genes
Cdk4,6/cyclin D then induces ___ ___ expression via the transcription factor E2F.
cyclin E
Cdk4,6/cyclin D then induces cyclin E expression via the transcription factor ___.
E2F
E2F-mediated transcription is inhibited by ___. ___ is phosphorylated by Cdk4,6/cyclin D. ___ releases E2F, activating it.
Rb, Rb, Rb
___/___ ___ induces entry into S phase.
Cdk2/cyclin E
Rb is a type of ___ ___ ___, a gene whose inactivation leads to tumor development.
tumor suppressor gene
___ ___ and the ___ ___ ___ (ORC) bind to replication origins during G1.
MCM helicase, origin recognition complex (ORC)
___/___ ___ activates the origin recognition complex (ORC) by phosphorylating activating proteins.
Cdk2/cyclin E
Cell cycle arrest occurs due to ___ of Cdk1 and Cdk2.
inhibition
___ and ___ are inhibitory kinases of Cdk1 and Cdk2.
Thr-14, Tyr-15
___ family = A family of phosphatases that REMOVE inhibitory phosphorylation by Thr-14 and Tyr-15.
Cdc25 family
DNA damage checkpoints are mediated by protein kinases ___ and ___.
ATM, ATR
ATM and ATR then phosphorylate and activate the checkpoint kinases ___ and ___.
Chk1, Chk2
Chk1 and Chk2 then inhibit ___, which leads to phosphorylation of Cdk’s, and arrest of the cell cycle.
Cdc25
Inhibition of Cdk2 results in cell cycle arrest in ___ and ___.
Inhibition of Cdk1 results in arrest in ___.
G1 and S, G2
In mammalian cells, ATM and Chk1 also mediate cell cycle arrest by the protein ___.
p53
Chk1 phosphorylates p53, stabilizing it, leading to the expression of the protein ___ = An inhibitor of Cdk2/cyclin E.
p21
Reminder: p21 is a ___ ___ (CKI)
Cdk inhibitor (CKI)
The p53 gene is frequently mutated in human ___. Loss of p53 prevents cell cycle arrest in response to DNA damage, so the damaged DNA is replicated and passed on to daughter cells.
cancers
