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Protein disables p53, drives breast cells toward cancer transition
Date:12/15/2010

HOUSTON - The recently identified TRIM24 protein plays an active role in pushing normal breast cells into rapid cell proliferation and, potentially, into breast cancer.

Reporting in the journal Nature, a team led by researchers at The University of Texas MD Anderson Cancer Center found that TRIM24 (tripartite motif-containing 24) pushes estrogen-responsive genes toward active expression. This expression, in turn, sets the stage for malignant transformation of breast cells. TRIM24 functions by reading a specific code, or signature, present at estrogen-regulated genes and recruiting estrogen receptors for gene activation. About 70 percent of breast cancers are estrogen receptor positive; their growth is driven by the hormone estrogen.

Tumor-suppressor labeled for destruction

TRIM24 is a chromatin regulator that normally maintains the tumor suppressor p53 at low levels until it is summoned to reduce cellular stress or DNA damage in cells. Abnormally high expression of TRIM24, however, suppresses p53 levels, making cells more vulnerable to the types of cellular damage that lead to cancer. In breast cells, high levels of TRIM24 also stimulate estrogen receptor activity, delivering a one-two punch that fuels cell proliferation and growth.

"We found that TRIM24 negatively regulates p53 by placing ubiquitin on it and thereby labeling it for destruction," said Michelle C. Barton, Ph.D., professor in the Department of Biochemistry and Molecular Biology at MD Anderson. "Two of TRIM24's structural domains indicated that it probably interacts with proteins called histones that spool DNA into chromatin. TRIM24 is an interpreter of specific modifications placed on histones that function like a barcode - we call this the histone code or histone barcode." TRIM24 then reads the particular barcode that the histone modifications spell out, receiving its instructions on such things as whether to activate a gene.

Barton added
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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