Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms

A Satyanarayana1, P Kaldis

  • 1Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA. satya@ncifcrf.gov

Oncogene
|June 30, 2009
PubMed

Insights

Cyclin-dependent kinases (Cdks) and cyclins exhibit compensatory mechanisms in cell-cycle regulation. Notably, Cdk2 is dispensable, with Cdk1 and Cdk4 compensating for its functions in mammalian cell division.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The classical model of cell-cycle regulation has been challenged by recent findings.
  • Gene knockout mouse models have revealed unexpected compensatory mechanisms among cell-cycle regulators.

Purpose of the Study:

  • To review compensatory mechanisms among major cyclins and cyclin-dependent kinases (Cdks) in mammalian cell-cycle regulation.
  • To highlight the dispensability of Cdk2 and the conserved nature of cell-cycle control.

Main Methods:

  • Review of existing literature on gene knockout mouse models.
  • Analysis of studies investigating compensatory mechanisms in cyclins and Cdks.
  • Examination of Cdk1's role in driving the mammalian cell cycle.

Main Results:

  • Cdk2 is dispensable for mitotic cell-cycle regulation in mammals.
  • Cdk4 and Cdk1 compensate for Cdk2's functions.
  • Cdk1 alone can drive the mammalian cell cycle, similar to yeast.

Conclusions:

  • Mammalian cell-cycle regulation is highly conserved, with Cdk1 playing a central role.
  • Compensatory mechanisms among Cdks and cyclins are crucial for cell-cycle control.
  • Cell-cycle-independent functions of Cdks and cyclins, including DNA damage repair, require further investigation.

Related Concept Videos

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.
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
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...