Protein Stops P53 In Its Tracks In Cancer Cells

However, precisely how HMGA1 mediates its pro-tumorigenic effects on p53 have not been clearly established.

Now, researchers from the Istituto Nazionale dei Tumori Regina Elena, Italy, show that in human cancer cell lines, HMGA1 inhibits p53-mediated apoptosis by interfering with the protein HIPK2, which helps p53 initiate apoptotic cell death.

In the study, which appears online on February 8 in advance of publication in the March print issue of the Journal of Clinical Investigation, Silvia Soddu and colleagues found that overexpression of HMGA1 inhibited p53-mediated apoptosis and caused HIPK2 to relocate from the cell nucleus to the cytoplasm. Further, expression of HIPK2 was required for HMGA1 to inhibit p53-mediated apoptosis.

Importantly, 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 mechanism by which p53-mediated apoptosis can be inhibited, leading to the development of cancer.