ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)
1Department of Pharmacology, KEIO University School of Medicine, Tokyo, Japan.
European Journal of Biochemistry
|December 26, 2001
Summary
p70ik3-1, a protein with a cyclin box, binds to p35cdk3 but does not activate cdk3. This study shows p70ik3-1 is phosphorylated by cyclin-dependent kinases, identifying it as a substrate for cdk3-mediated phosphorylation.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- p70ik3-1 is a 70-kDa protein containing a cyclin box.
- It binds to p35cdk3 in vivo and in vitro.
- Despite structural similarity to cyclins, p70ik3-1 does not activate cdk3-mediated phosphorylation of key substrates like pRb.
Purpose of the Study:
- To investigate the functional role of p70ik3-1 in relation to cyclin-dependent kinases (CDKs).
- To determine if p70ik3-1 itself is a substrate for CDK-mediated phosphorylation.
Main Methods:
- In vitro phosphorylation assays using purified proteins.
- Expression and co-expression studies in COS7 cells.
- Analysis of p70ik3-1 phosphorylation at Ser274.
Main Results:
- Serine 274 (Ser274) of p70ik3-1 is phosphorylated by cdk2 and cdk3 when bound to cyclin A or cyclin E in vitro.
- Ectopic co-expression of cyclin E and cdk3 in COS7 cells leads to increased phosphorylation of Ser274 in p70ik3-1.
- These findings indicate that p70ik3-1 is a direct substrate for cdk3.
Conclusions:
- p70ik3-1 is a substrate for cdk3-mediated phosphorylation.
- The phosphorylation site is identified as Ser274.
- This clarifies a functional aspect of p70ik3-1 beyond its structural similarity to cyclins.
Related Concept Videos
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
02:39Positive 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.
02:34Inhibition 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...
02:15M-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...
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...
02:34Inhibition 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...
02:15M-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...
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...