Finding familiar pathways in kidney cancer

From Phys.Org:

p53 is the most famous cancer gene, not least because it’s involved in causing over 50% of all cancers. When a cell loses its p53 gene—when the gene becomes mutated—it unleashes many processes that lead to the uncontrolled cell growth and refusal to die, which are hallmarks of cancer growth. But there are some cancers, like kidney cancer, that that had few p53 mutations. In order to understand whether the inactivation of the p53 pathway might contribute to kidney cancer development, Haifang Yang, Ph.D., a researcher with the Sidney Kimmel Cancer Center—Jefferson Health probed kidney cancer’s genes for interactions with p53.

Earlier work found that PBRM1—the second most mutated gene in kidney cancer—could interact with p53. However, other researchers were unable to definitively show that it was truly an important mechanism in kidney cancer. Rather than looking at the p53 protein itself, first author Weijia Cai a postdoc in Dr. Yang’s lab and other collaborators looked at an activated version of p53, one that is studded with an additional chemical marker—an acetyl group—at many specific spots. In a paper published in Nature Communications, on Friday December 20th, Dr. Yang, an assistant professor of Pathology, Anatomy and Cell Biology at Jefferson examined whether PBRM1 can be a “reader”, or translator, of the activated p53. They noticed—by the help of a number of biochemical and molecular tests using both human cancer cell lines and mouse and human tumor samples—that PBRM1 uses its bromodomain 4 to bind to p53, but only in its activated form, with the acetyl group in one specific spot. Tumor-derived point mutations in bromodain 4 can disrupt this interaction, and the resulting mutant PBRM1 loses its ability to suppress tumor growth. The research suggests that the second-most highly mutated gene in kidney cancer, is strongly linked to a well-studied and understood cancer pathway.

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