Advanced Cell Bio Final

Cell cycle

four coordinated processes that leads to cellular duplication: reproduction

S phase

synthesis of DNA, in this phase the DNA is duplicated

M phase

mitosis, the chromosomes segregate into the daughter cells

G1 phase: Gap phase 1

the cell physically grows, if proper environmental conditions are met, the cell enters S phase (commitment)

G2 phase: Gap phase 2

the cell continues to grow, proteins and organelles are made, preparation to mitosis (cell division)

checkpoints

in eukaryotes control mechanisms dictate the cell cycle progression at three points

G1/S checkpoint

the cell commits to cell duplication, checking for environmental favorable conditions to replicate

G2/M checkpoint

mitotic entry and alignment of chromosomes on the metaphase plate, checking for DNA errors

M/G1 checkpoint

Metaphase to anaphase transition. Stimulation of chromosome separations and cytokinesis. Checking for correct chromosomes alignment

cyclin binding activates

Cdk

cyclin-dependent kinases govern

cell cycle progression

Cdks are not active until

cyclins bind to them

CdKs are

constantly expressed during the cell cycle

cyclins expression

changes throughout the cell cycle

How is the CdK-cyclin complex activated

when the cyclins bind to the CdKs

CdK-cyclin complexes

phosphorylate target proteins that govern the cell cycle progression

CKI bindings switches

off the Cdk/Cycin complex

CKI controls the activities of

G1/S complexes and early S complexes

CKI bind to both

CdK and cyclin, distorting their activities to not be able to target protein anymore

APC (Anaphase promoting complex)

promote cytokinesis, APC is active in mid-mitosis and G1, APC target S and M cyclins because it changes throughout the cell cycle

APC is a member of the

ubiquitin family (proteins are tagged with ubiquitin for degradation)

APC promotes the

destruction of securing (chromosomes separation) and target S phase cyclins

Activation of APC depends on

CDC20 and Cdh1

SCF

belongs to the ubiquitin family, targets CKI promoting S phase and DNA synthesis, targets S phase cyclins

inhibitory phosphorylation

turns off CdK/Cyclin activity

Wee1

kinase that phosphorylates CdK (inactive Cdk/cyclin complex)

Dephosphorylation of Cdk-M cyclins promotes

entry in mitosis

activity of Cdc25 promotes

dephosphorylates CdK, activation of Cdk-M cyclins, leading to mitosis

Activation of Cdk-M complex

accumulation of M cyclins during G2 (gonna bind to CdK)

inhibitory phosphorylation by Wee1

activation of Cdk-M by the phosphatase Cdc25

how does activation of Cdk-M promote positive feedback?

Cdk-M complex inhibits the phosphatase PP2A-B55 promoting increase of the CDC25 phosphorylated species

Cdk-M complex inhibits the phosphatase PP2A-B55 promoting the activity of Wee1

(inhibition of its inhibitor Wee1 and activation of its activator Cd25)

PP2A-B55 is an

inhibitor of Cdk-M complex