Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E

J C de Nooij1, K H Graber, I K Hariharan

  • 1Massachusetts General Hospital Cancer Center, Building 149, Charlestown, MA 02129, USA.

Mechanisms of Development
|October 12, 2000
PubMed

Insights

Cyclin E accumulation drives the expression of Dacapo, a cell cycle inhibitor, in Drosophila. This discovery reveals a key mechanism controlling cell division arrest before differentiation.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • The Cip/Kip family of cyclin-dependent kinase inhibitors (CKIs) are crucial for cell cycle arrest preceding terminal differentiation.
  • The precise mechanisms activating CKI expression during this process remain largely unknown.

Purpose of the Study:

  • To investigate the regulatory mechanism of dacapo, a Drosophila Cip/Kip CKI, during cell cycle arrest.
  • To elucidate the relationship between Cyclin E and Dacapo expression.

Main Methods:

  • Analysis of dacapo RNA and protein accumulation in Drosophila.
  • Investigating the effect of Cyclin E overexpression on dacapo expression.
  • Studying the temporal coupling of Cyclin E and Dacapo during ovarian endocycles.

Main Results:

  • Dacapo RNA and protein accumulation is dependent on Cyclin E.
  • Increased Cyclin E expression can induce dacapo expression.
  • Cyclin E and Dacapo protein levels oscillate in tight coordination during ovarian endocycles.

Conclusions:

  • Cyclin E/Cdk activity plays a critical role in inducing Dacapo expression.
  • Dacapo expression is regulated within specific temporal windows permissive for its induction by Cyclin E/Cdk activity.

Related Concept Videos

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.
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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.
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...
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...
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...