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Cyclin Dependent
Kinases
What are CDKs?
 Cyclin-dependent kinases (CDKs) are protein kinases involved
in critical cellular processes.
 They are important in the regulation and control of cell cycle.
 They are also involved in regulating transcription, mRNA
processing, and the differentiation of nerve cells.
 They are always present in the cells in their inactive form , but
the binding of a cyclin activates it, making it a functional
enzyme and allowing it to modify target proteins.
 CDKs are the enzymes that phosphorylates specific target
proteins and the attached phosphate group acts like a switch,
making the target protein more or less active.
Checkpoints of cell cycle:
Cyclin and CDK complexes
present in different phases :
Working mechanism:
Cyclin dependent kinases
Cyclin dependent kinases
cyclinE,A
CDK2
P- p27kip1
 Tumor suppressor protein retinoblastoma (Rb) protein holding
transcription factor E2F.
 cyclin_-CDK complex phosphorylate the Rb protein and leads
the release of E2F.
 E2F can then activate transcription of the cyclin E gene. Cyclin
E binds CDK2, and this complex fully phosphorylates Rb,
completing its inactivation. Cyclin E also phosphorylates
p27Kip1, an inhibitor of Cyclin D. Phosphorylation of p27Kip1
tags it for degradation. Degradation of this protein promotes
expression of cyclin A.
 During S phase, Cyclin A ensures that DNA replication only
occurs ONCE per cell cycle by preventing assembly of
excessive replication complexes.
 The Cyclin A-CDK2 complex also regulates DNA replication by
phosphorylating certain DNA replication machinery
components.
 When the cell transition occur to M phase cyclin A gets
replaced with cyclin B.
 Cyclin B is a mitotic cyclin which binds to CDK1 to form the
maturation promoting factor, or mitosis promoting factor . The
concentration of MPF rises until mitosis, until its concentration
falls abruptly due to degradation of Cyclin B. High
concentrations of Cyclin B are necessary for cells to enter M
phase, and low concentrations are needed to exit M phase.
 When DNA damage is their cyclin cdk inhibitors gets activated
i.e. Tumor suppressor proteins like p53,p21,p27kip1 etc.
 P53 activates p21 and binds all cyclin cdk complexes and
activity of Rb proteins get restored and E2F is inactivated .
 Transcription gets halt and cell gets time for the repair of DNA
damage.
Cyclin dependent kinases
Cyclin dependent kinases
References :
 https://youtu.be/VLJF8Pf8spw
 https://youtu.be/nEMMKzYQf9A
 Nelson and Cox Lehninger principles of biochemistry 6th
edition (chapter no.12)
 https://www.khanacademy.org/science/ap-biology/cell-
communication-and-cell-cycle/regulation-of-cell-cycle/a/cell-
cycle-regulators
Thank you!

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Cyclin dependent kinases

  • 2. What are CDKs? Cyclin-dependent kinases (CDKs) are protein kinases involved in critical cellular processes. They are important in the regulation and control of cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are always present in the cells in their inactive form , but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins. CDKs are the enzymes that phosphorylates specific target proteins and the attached phosphate group acts like a switch, making the target protein more or less active.
  • 4. Cyclin and CDK complexes present in different phases :
  • 9. Tumor suppressor protein retinoblastoma (Rb) protein holding transcription factor E2F. cyclin_-CDK complex phosphorylate the Rb protein and leads the release of E2F. E2F can then activate transcription of the cyclin E gene. Cyclin E binds CDK2, and this complex fully phosphorylates Rb, completing its inactivation. Cyclin E also phosphorylates p27Kip1, an inhibitor of Cyclin D. Phosphorylation of p27Kip1 tags it for degradation. Degradation of this protein promotes expression of cyclin A. During S phase, Cyclin A ensures that DNA replication only occurs ONCE per cell cycle by preventing assembly of excessive replication complexes.
  • 10. The Cyclin A-CDK2 complex also regulates DNA replication by phosphorylating certain DNA replication machinery components. When the cell transition occur to M phase cyclin A gets replaced with cyclin B. Cyclin B is a mitotic cyclin which binds to CDK1 to form the maturation promoting factor, or mitosis promoting factor . The concentration of MPF rises until mitosis, until its concentration falls abruptly due to degradation of Cyclin B. High concentrations of Cyclin B are necessary for cells to enter M phase, and low concentrations are needed to exit M phase.
  • 11. When DNA damage is their cyclin cdk inhibitors gets activated i.e. Tumor suppressor proteins like p53,p21,p27kip1 etc. P53 activates p21 and binds all cyclin cdk complexes and activity of Rb proteins get restored and E2F is inactivated . Transcription gets halt and cell gets time for the repair of DNA damage.
  • 14. References : https://youtu.be/VLJF8Pf8spw https://youtu.be/nEMMKzYQf9A Nelson and Cox Lehninger principles of biochemistry 6th edition (chapter no.12) https://www.khanacademy.org/science/ap-biology/cell- communication-and-cell-cycle/regulation-of-cell-cycle/a/cell- cycle-regulators