(ChemotherapyAdvisor) – New insights into the function of a tumor control protein could lead to a novel cancer drug target, according to a team of researchers of Case Western Reserve University, Cleveland, OH. This conclusion is based on a study entitled “Autoregulatory Mechanisms of Phosphorylation of Checkpoint Kinase 1,” which was published in Cancer Research on August 1.
Normal cells divide for a finite amount of time, and then die. On the other hand, cancer cells continue to divide unabated, becoming immortal. Cells divide during what is known as the cell cycle. This cycle is controlled at certain points called checkpoints, where the “decision” to divide or not to divide depends on the state of DNA in the cell; the more DNA damage a cell contains, the less likely it will divide. That is cell division in normal cells.
In normal cells, cell cycle checkpoints are controlled by specific checkpoint proteins. Checkpoint protein function is aberrant in cancer cells, thus differentiating them from normal cells. Aberrant checkpoint control leads to tumor development. Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, is one of several checkpoint proteins charged with guarding cell-cycle checkpoints. Chk1 is itself activated by the kinase ATR in response to DNA damage. In this study, the investigators aimed to determine the precise molecular mechanisms controlling Chk1 activation.
Several results from this study enabled the investigators to meet this aim. First, they found that, in response to cellular DNA damage, ATR activates Chk1 by phosphorylating 2 of its specific serine amino acids. Second, the investigators showed that, in the absence of DNA damage, Chk1 inactivates itself, thus preventing ATR from activating it. These checkpoint control mechanisms enable the normal cell to avoid dividing before repairing its DNA damage, thereby preventing the development of new tumors and the continued growth of existing tumors.
The investigators concluded that the findings presented in this study could lead to the development of a novel strategy to suppress tumor growth.