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Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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CDK5 interacts with Slo and affects its surface expression and kinetics through direct phosphorylation.

Jun-Ping Bai1, Alexei Surguchev, Powrnima Joshi

  • 1Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.

American Journal of Physiology. Cell Physiology
|November 19, 2011
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Cyclin-dependent kinase 5 (CDK5) interacts with the Slo α-subunit of large-conductance calcium-activated potassium (BK) channels. CDK5 regulates BK channel surface expression and kinetics in hair cells, impacting electrical tuning.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Otolaryngology

Background:

  • Large-conductance calcium-activated potassium (BK) channels, composed of Slo α-subunits and accessory subunits, are crucial for electrical tuning in auditory hair cells.
  • BK channel kinetics and expression vary along the tonotopic axis, but their molecular regulation in hair cells remains unclear.

Purpose of the Study:

  • To identify novel interacting partners of the Slo α-subunit involved in BK channel regulation in hair cells.
  • To investigate the role of cyclin-dependent kinase 5 (CDK5) in regulating BK channel function and expression.

Main Methods:

  • Co-immunoprecipitation to identify CDK5 as a Slo-interacting partner.
  • Immunohistochemistry to determine CDK5 localization in hair cells.
  • Electrophysiology and Western blotting in human embryonic kidney cells to assess the effect of CDK5 on Slo channel activity and surface expression.

Main Results:

  • CDK5 was identified as a novel interacting partner of the Slo α-subunit.
  • CDK5 is expressed in hair cells, particularly in the cuticular plate and circumferential zone.
  • CDK5 directly phosphorylates Slo at T847, inhibiting surface expression and altering voltage activation/deactivation kinetics.

Conclusions:

  • CDK5 directly regulates the surface expression and gating kinetics of BK channels via phosphorylation of the Slo α-subunit.
  • The tonotopic expression pattern of CDK5 suggests its critical role in electrical tuning and frequency discrimination in hair cells.