doi:10.1038/nindia.2010.65 Published online 24 May 2010
Whether a cancer cell will stop growing or will undergo programmed cell death is decided by a tumor suppressor gene p53. Researchers have now unravelled the mechanism by which p53 bifurcates these two processes with help from the nuclear matrix associated protein SMAR1.
The p53 tumor suppressor gene plays an important role in preventing cancer development, by arresting or killing potential tumor cells. Researchers have been trying for long to understand the role of the nuclear matrix associated protein SMAR1 in several pathophysiological processes.
The team had earlier shown that the tumor suppressor protein SMAR1 works synergistically with p53 to inhibit cell proliferation. The p53 exerts its tumor suppressor functions mainly by transcriptional regulation of its target genes, resulting in either growth arrest or programmed cell death (apoptosis). The genes involved in induction of cellular arrest or apoptosis are controlled by p53. How p53 differentially regulates these genes and controls these two processes is a long standing question.
The researchers have now shown that the fine tune regulation of cell cycles arrests and induces apoptosis in cancer cells. "We found that p53 induces the expression of two transcription factors SMAR1 and PML at different extents of DNA damage to dictate the cell fate towards arrest or apoptosis," says lead researcher Samit Chattopadhyay.
The tripartite nexus of p53, SMAR1 and PML is required to drive cells toward apoptosis. It is interesting to note that SMAR regulates p53 on one hand and is a transcriptional target of p53 on the other. "So there exists a feedback loop. This has tremendous implication in cancer cases where p53 is mutated and SMAR1 expression is compromised. Restoring SMAR1 function can inhibit cancer cell proliferation," he adds.
A small molecule or compound that can induce SMAR1 level in cancer cells could, therefore, have therapeutic potential.
The authors of this work are from: National Centre for Cell Science (NCCS), Pune, Department of Biotechnology, University of Pune & Virology Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India.