cyclin dependent kinases and complete information - Mandira bhosale.

1. Cyclin Dependent
Kinases

2. What are CDK’s?
• 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.
• CDK’s 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.

3. Checkpoints of cell cycle:

4. Cyclin and CDK complexes
present in different phases :

5. Working mechanism:

8. cyclinE,A
CDK2
P- p27kip1

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

15. Thank you!