cell cycle.txt

• G1
• S
• G2
• Mitosis

• Regulatory proteins:
• 1. Cyclin
• 2. Cyclin-Dependent kinases (CDKs)

• Cells INCREASE in size
• New organelles produced
• New proteins produced
• Cdk inhibitor DEGRADED

Formation of: Cyclin E and cdk2

• CDK2 phosphorylates cyclin E
• Phosphorylated CyclinE/CDK2 complex Phosphorylates a tumor suppressor protein RB1
• This causes RELEASE of EF2
• Once Cyclin E duties are done, it is ubiquitinated and degraded via proteasome

• Phosphorylates T loop
• Needed to Activate Cyclin E and cdk2

• PRODUCES Cyclin E
• Activates genes whose protein products are required for transition from G1>> S phase
• 
Role of cyclin D/Cdk4,6,
• Involved with INITIATION of signals prior to ENTRY of S phase
• This complex Phosphorylates Rb, which ALLOWS EF2 to activate genes required for transition from G1 >> S phase
• Also with Cmyc

Rapid Cell growth and Protein synthesis, prior to Mitosis

Ensures DNA replication has completed during S phase

• Maturing-promoting factor: Cyclin-cdk complex that triggers cell passage PAST G2 checkpoint
• Consists of Cyclin B complex with cdk1 or 2
• 3 residues must be activated on this complex for G2M to occur
• 1. Cdk1 must be Phosphorylate threonine by Cyclin activating kinase (CAK)
• 2 and 3. To ACTIVATE cyclin B/cdk1, cdc25 must remove phosphate on threonine and tyrosine and ADD hydroxy group
• Activity HIGH during M phase

On each kinetichore, once microtubules are captured and tension detected, Mad2 is released

• Mitotic motor protein: Uses ATP hydrolysis to drive transport of cellular cargo along microtubules
• 1. essential for attachment of chromosomes (via kinetichore) to spindle microtubules
• 2. Helps chromosomes CONGREGAGE @ equatorial plane and STABILIZE
• 3. Helps develop TENSION across aligned chromosomes

• BubR1 (checkpoint kinase) and Bub3 are partiall RELEASED
• Mad2 is blocked: SILENCES Spindle assembly checkpoint upon proper microtubule kinetichore attachment
• This PREVENTS INHIBITION of Anaphase-promoting complex (APC)

• Spindle checkpoint PROTEIN
• Provides biochemical signal to proceed to ANAphase, by being released
• Mad2 required to activate APC/C to go into Anaphase
• Mad2 bound to CDC20 will NOT activate APC/C

• Mutations in Mad2 can cause DISRUPTIONS in Spindle Assembly Checkpoint (SAC)
• Decrease in Mad2: Inactivation, can result in aneuploidy, which results in TUMOR formation (via unregulated cell growth)
• Mad2 OVERexpression: Stabilizing proteins DELAY exit from mitosis, cause aneuploidy

assembly Recruitment of CENP-E and Mad2

enzyme that Degrades COHESION, allowing ANAPHASE to progress

Look at diagram ONLINE

• + ends of microtubules attach to sister kinetichores and ALIGN sister chromatids on plane
• Creates TENSION

Microtubules elongate, helping PUSH spindle poles apart