KINE 1000 Lecture Notes - Lecture 6: Phosphorylation, Helicase, Proteolysis
4 Jun 2018
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APC/C atalyzes uiuitylatio &
destutio of two ajo types of poteis
o Securin: holds sister chromatids in early mitosis. Destructions activates a
protease that separates sisters & allows anaphase
o S & M cyclins: destroying these cyclins inactivates cdks. Proteins are
dephosphorylated by phosphatase in anaphase. Dephosphorylation of cdk
targets is required for completions of M-phase
• APC/C remains active in G1 to provide stable cdk inactivity
• G1/S-cdk is activated in late G1, APC/C is turned off to allow cyclin accumulation
• Ubiquitin ligase called SCF ubiquitylates certain CKI proteins in late G1- controls
activation of s-cdks & DNA replication units
• APC/C activity changes during cell cycle as it associated with activating subunits –
cdc in mid mitosis or cdh1 from late mitosis/early G1. Subunits help APC/C
recognize target proteins
Cell Cycle Depends on Transcriptional Control
• Post-transcriptional mechanisms involves regulation of cdks & ubiquitin ligases &
target proteins
• Transcriptional controls provides additional level of regulation
• Changes in cyclin gene transcription helps control cyclin levels in most cells
Cell-Cycle Control & Biochemical Switches
• Activation of series of biochemical switches – each triggers specific cell-cycle
events
• When conditions for cell proliferation are right, various external & internal
signals stimulates activation of G1-cdk, which stimulates expression of genes
encoding G1/S- & S-cyclins
• G1/S-cdk drives progression through start transition & initiates chromosome
duplication
• M-cdk activation triggers progression through G2/M transition & events of early
mitosis – leading to alignment of sister-chromatid pairs
• APC/C & activator cdc20 triggers destruction of securing & cyclins
o Allows sister-chromatid separation & completion of mitosis
• After mitosis is complete, multiple mechanisms wok to supress cdk activity to
give stable G1 period
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