Mitotic Regulation

• Cyclins and Cyclin-dependent Kinases

  • G1 = Cdk4, 6 / CycD
  • S = Cdk2 / CycE
  • G2 to M = Cdk1 / CycB
• Cyclins and Cyclin-dependent Kinases

  A) Cdk1

  B) CycA

  C) Cdk1

  D) CycB

  E) Cdk4

  F) Cdk6

  G) CycD

  H) Cdk2

  I) CycE

  J) Cdk2

  K) CycA

  
• Cdk inhibitors

  • P27 - inhibits Cdk2 / Cyclin E (important for S-phase)
  • P21 - inhibits Cdk2 / CycE (G2 to M phase)
  • Wee1 - inhibits Cdk1 (phosphorylates)(inhibits)
  • CycD - Cdk 4, 6
  • CycE - Cdk 2
  • CycB - Cdk 1
• Cdc phosphatase (cell division cycle) (activators)

  • Cdc25 - dephosphorylates Cdk1
  • Cdc20 - dephosphorylates APC/C
• Ubiquitin ligase

  • APC/C - anaphase promoting complex/cyclosome
• Stages of mitosis

  • Prophase
  • Metaphase
  • Anaphase
  • Telophase
• T or F: Cdk4,6/CycD is not a GF-dependent

  False
• Cdk1/CycB is inhibited by Phos-Tyr15 and/or -Thr14
• T or F: Interphase happens during G1 to S phase transition

  False
• The G1, S, and G2 phases of interphase are periods of growth and preparation for mitosis
• What are found in G1 Phase?

  Growth factors and Cdk4, 6 / CycD
• What are found in S phase?

  Centrosome duplicates

  Dna replicates - Cdk2/CycE

  Checkpoint 1
• What are found in G2 phase?

  Checkpoint 2

  Ckd1/CycB
• In mitotic regulation (cell division), phosphorylation is used as an activation mechanism
• RTK = receptor thyrosine kinase
• RAF = rapidly accelerated fibrosarcoma
• MAPK (KK) = Mitogen activated protein kinase (kinase kinase)
• Growth factors (G1 Phase)

  • RAF = MAPKKK
  • MEK = MAPKK
  • ERK = MAPK
• ERK = extracellular signal regulated kinase
• G1 Phase (use acronyms)

  A) GF

  B) RTK

  C) RAF

  D) RAS

  E) MAPK

  F) ERK

  G) AKT

  H) TF

  I) TF

  J) CycD

  K) Cdk4, 6

  L) CycD

  
• T or F: Cell moves pass through G0 even if there are no Cdk4,6/CycD

  False
• APC/C = anaphase promoting complex/cyclosome
• T or F: CycE is inhibited by p27

  True
• T or F: Passing through the restriction point induces the synthesis of CycE via activation of E2F, this results in the activation of Cdk2 wherein it does dephosphorylates and targets p27 for degradation

  False
• T or F: Cdk2/CycE inhibits APC/C ubiquitin ligase thus prevents CycE degradation

  True
• S phase and regulation of DNA replication (use acronyms)

  A) ORC

  B) MCM

  C) Cdk2

  D) CycE

  E) DDK

  F) MCM

  G) MCM

  H) Replication fork

  
• Question to ask during cell division (checkpoints)

  • S/G2 phases checkpoint - are there double stranded breaks? Is the cell large enough?
  • G2 to M checkpoint - is the cell ready to divide?
  • Metaphase/Anaphase checkpoint - is the formation of spindle with microtubule proper?
• Phosphorylation during G2 to M

  A) Chromatin condensation

  B) Nuclear envelope breakdown

  C) Golgi apparatus fragmentation

  D) Spindle formation

  
• Untangling and condensation of chromosomes consisting of 2 sister chromatids happens during?

  Prophase
• Sister chromatids held in centromere, where proteins bind to form the kinetochore
• During the late phase of prophase, nuclear membrane breakdown which happens due to phosphorylation of lamins
• T or F: phosphorylation of condensins and cohesins will induce sister chromatids


  True
• What stage of cellular division is the binding of microtubule spindle to kinetochore?

  Prometaphase
• What stage of cellular division is the alignment of DNA chromosomes in the middle?

  Metaphase
• What is the stage of cellular division where sister chromatids detach?

  Metaphase
• What is the stage of cellular division where chromosome associated kinesins pull chromosomes to (-) centrosome?

  Anaphase
• Dynein in astral microtubules pulls centrosomes to opposite poles
• What stage in cellular division is where nuclear membrane reforms and chromosome decondenses?

  Telophase
• MLCK - Myosin light chain kinase
• When DNA becomes replicated, what checkpoint is it found?

  S/G2