Normal Function of Tumor Suppressor Rb

The Rb gene is essential for the normal functioning of the cell cycle. Cells respond to a variety of environmental factors that instruct them to grow and divide, rest, or undergo apoptosis. Disruption of these signals can lead to unregulated cell growth, which ultimately results in cancer. The control of the cell division process involves the integration of a variety of signals.

The Rb gene product (pRb) normally functions as a growth inhibitor by binding to and inhibiting transcription factors. Therefore, Rb indirectly controls the expression of a variety of genes. Some of these genes produce proteins involved in driving cell division forward. Thus, Rb activity slows or halts cell division.⁽¹⁾ Changes to regulatory proteins such as Rb can have dramatic effects on individual cells and ultimately the entire organism.Besides its involvement in regulation of the cell cycle, Rb also plays a role in apoptosis. Apoptosis is a very important cellular function in which a damaged cell undergoes programmed death. If a cell undergoes mutations that cannot be repaired, the cell can be eliminated via apoptosis. This process eliminates cells that have the potential for unregulated, potentially cancerous, growth. Any alterations in cellular function that reduce or eliminate the activation of apoptosis may have deleterious effects on the cell population.⁽²⁾ The Rb gene may be inactivated via several different types of genetic damage. Mutations that completely eliminate the function of the protein (null mutations) are often seen in cells without functional Rb protein.

A Closer Look at Rb's Functions

In addition to its role regulating cell growth and apoptosis, recent studies indicate that proteins related to Rb can have differential activity depending upon the stage of the cell cycle and their location within the nucleus. Further, some studies indicate that Rb-like proteins can regulate transcription of rRNA and tRNA, meaning that pRBs can exert control over both transciptional and posttranscriptional events in cells.⁽³⁾

In addition to its role as a transcription factor, pRb has also proven to have additional activities that may contribute to its tumor suppressive effects. The Rb protein has been shown to associate with chromatin modification proteins such as histone deacetylases (HDAC). HDACs are thought to affect transcription by removing acetyl groups from histones. This modification results in a closer association between DNA and nucleosomes. ⁽⁴⁾ The closer DNA:histone interaction makes it more difficult for transcription( )factors like E2F to bind to their target regions in the DNA. It still remains unclear what Rb's function is in this process, but studies have shown that at least some HDACs do not function properly in the absence of Rb. ⁽⁵⁾

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Last Modified: 08/31/2010

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References for this page:

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