Protein Found to Suppress p53 in Cancer Cells

For the first time, researchers have demonstrated that in human cancer cell lines, a protein known as HMGA1 inhibits p53-mediated apoptosis by interfering with the protein HIPK2, which helps p53 initiate apoptotic cell death.

Overexpression of HMGA1 has been associated with many types of cancer in humans. Earlier research has shown that HMGA1 decreases the ability of p53 to inhibit cell death by a process known as apoptosis; inhibition of p53-mediated apoptosis causes tumors to develop in both animals and humans. However, precisely how HMGA1 mediates its pro-tumorigenic effects on p53 have not been clearly established.

In the study, which appears online on February 8, 2007, in advance of publication in the March 2007 print issue of the Journal of Clinical Investigation, Dr. Silvia Soddu and colleagues, from the Istituto Nazionale dei Tumori Regina Elena (Rome, Italy), found that overexpression of HMGA1 inhibited p53-mediated apoptosis and caused HIPK2 to relocate from the cell nucleus to the cytoplasm. Furthermore, expression of HIPK2 was required for HMGA1 to inhibit p53-mediated apoptosis.

Significantly, analysis of human breast cancer samples indicated that overexpression of HMGA1 correlated with the presence of HIPK2 in the cytoplasm and low levels of apoptotic cells, even in the presence of normal p53. This study therefore identifies a new process by which p53-mediated apoptosis can be suppressed, leading to the development of cancer.


Related Links:
Istituto Nazionale dei Tumori Regina Elena