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44 Cards in this Set

  • Front
  • Back

Cell cycle

Series of steps that lead to cell division

Function of cell cycle

- Accurately duplicate DNA of chromosome


- Precisely segregate sister chromatids into two daughter cells

Accurately duplicate DNA of chromosome

Function of cell cycle (1)

Precisely segregate sister chromatids into two daughter cells

Function of cell cycle (2)

Cell cycle control system

- Comprised of regulatory proteins


- Govern progression through cell cycle


*(checkpoints)

Checkpoints

*cell cycle control system


- govern progression through cell cycle


- comprised of regulatory proteins

Mechanics of cell division

- Mitosis


- Cytokinesis

Mitosis

*Phase of cell division (mechanics)


- separation of sister chromatids

Mitotic spindle

*part of mitosis


- Made of


--Microtubules (MTs)


--MT associated proteins (MAPs)


-- MT dependent motor proteins (kinesin-related proteins/dyneins)

MT dependent motor proteins

*make up part of mitotic spindle


- Kinesin related proteins


- Dyneins

Cytokinesis

*Phase of cell division (mechanics)


- division of cytoplasm

Contracting ring

*part of cytokinesis


- made of...


--Actin


--Myosin

Actin/myosin

Make up contracting ring of cytokinesis

Cell cycle control proteins

- Cyclin dependent kinases (Cdks)


- Cyclins

Cyclin dependent kinases (Cdks)

*cell cycle control protein


- Protein kinase--> control major cell cycle events


(replication, mitosis)


- Activity rises and falls during cell cycle

Cyclins

*cell cycle control protein


- Major regulator of Cdk activity


- binds Cdk directly


- Changes in level controls cdk activity


- different types in different phases of cell division


(ex. M-cyclin, Cyclin B)

M-Cdk

Cyclin-Cdk complex


- M-cyclin+Cdk1

Cdk activity regulation methods

*Regulation


- Phosphorylation


- Binding of cdk inhibitors


- Proteolysis of cyclins

Cdk activity regulated by phosphorylation

*cdk activity regulation


- Phosphorylation of T161/Y15 site


- important in control of M-cdk activity


--uses wee1, CAK, and cdc25

Cdk activating kinase (CAK)

*regulates cdk activity


- phosphorylates the top of Cdk protein (T161)


- makes M-Cdk active

Wee1

*regulates cdk activity


- Cdk inactivating kinase


- phosphorylates bottom of Cdk protein (Y15)


- makes M-Cdk inactive

Cdc25

*regulates cdk activity


- Protein phosphatase


- Dephosphorylates Y15


- Makes M-Cdk active

Active M-cdk

- promotes entry into mitosis

Inactive M-cdk

- inhibits mitosis entry


- promotes exit

Cdk activity regulated by binding of cdk inhibitors

*cdk activity regulation


- binds inhibitor on cdk+cyclin complex (m-cdk)


- makes m-cdk inactive


- important in control of G1-S phase


-- uses CKI

Cdk inhibitor protein (CKI)

*regulates cdk activity


- binds to M-cdk complex on top --> inactivates


- inhibits mitosis entry


Ex: p21, p29

CKI types

*regulates cdk activity


- P21


- P29

Cdk activity controlled by regulated proteolysis of cyclins

*cdk activity regulation


- Breakdown of cyclins with proteasomes


- Inactivates cdk


-- uses ubiquitin ligase

Proteasomes

- Degrades cyclins tagged by polyUbiq. chain

Ubiquitin ligase

*regulates/controls cdk activity


- recruits ubiquitin


- forms ubiquitin chain


- degrades cylins


--Ex: SCF, Anaphase promoting complex (APC)

Ubiquitin

*regulates/controls cdk activity


- recruited by ubiquitin ligase


- attaches to cyclin protein and forms polyubiquitin chain

Polyubiquitin chain

*regulates/controls cdk activity


- acts as tag for degradation by ubiquitin ligase

Examples of proteasomes

- SCF


- Anaphase promoting complex (APC)

SCF

*regulates cdk activity


- type of ubiquitin ligase


- degrades CKI


-- activates G1/S-cdk

Anaphase promoting complex (APC)

*regulates cdk activity


- type of ubiquitin ligase


- degrades M-cyclin and Securtin

Activation of M-cdks

- triggers entry into mitosis

M-cyclin (Cyclin B)

Activation of M-cdk begins with accumulation of...

Cyclin B

*M-cyclin


- activates M-cdk when accumulated


- levels oscillate during cell cycle

Interphase

*M-cdk activation


- Cell cycle that increases Cyclin B synthesis


- G1--> M-phase


-- triggers entry into mitosis

Anaphase

*M-cdk activation


- Cell cycle that degrades Cyclin B


- Cdk1 inactivation


-- triggers exit from mitosis

Positive feedback

*M-cdk activation


- Abrupt increase in Cdk/cyclin B activity


- Late in G2 phase


(Cyclin B level/Cdk1 activity relationship)

Cdk1/cyclin (M-cdk)

*M-cdk activation


- Activates Cdc25


- Inhibits Wee1

Activation of Cdk1/cyclin

*M-cdk activation


- irreversible and complete


- promoted by feedback loops

Regulation by Cdk1/cyclin B (M-cdk)

*regulation


- Assembly of mitotic spindle (motor proteins)


- MT dynamics (MAPs) (MT binding protein)


- Chromosome condensation (condensin)


- Nuclear envelope breakdown (nuclear lamins)