Scientists from Singapore have identified that in low oxygen stabilize Tap73 which is the homologous protein of p53. It can promote the angiogenesis process in tumor tissue and is very important to the growth of tumor. This study was published in Nature Cell Biology.

p73, a homologue of the p53 tumor suppressor, exists as two main forms: the full length TAp73 that exhibits tumor-suppressor functions and is capable of inducing cell death, and the DNp73 form that lacks the amino-terminal transactivation domain, and is incogenic through its ability to inhibit both TAp73- and p53-dependent tumor suppressive functions. The functional significance of the overepression of unmutated TAp73 in human cancers is still unclear, but raises the possibility of unidentified roles in promoting tumorigenesis.

In this study, researchers show that TAp73 is stabilized by hypoxia, a condition highly prevalent in tumors, through HIF-1α-mediated repression of the ubiquitin ligase Siah1, which targets TAp73 overexpression leads to increased vasculature.

Moreover, they show that TAp73 is a critical regulator of the angiogenic transcriptome and is sufficient to directly activate the expression of several angiogenic genes. Finally, expression of TAp73 positively correlates with these angiogenic genes in several human tumors, and the angiogenic gene signature is sufficient to segregate the TA73^Hi-from TAp73^Low-expressing tumors.

These data demonstrate a pro-angiogenic role for TAp73 in supporting tumorigenesis, providing a rationale for its overexpression in cancers.

Reference:

Dulloo I, Phang B H, Othman R, et al. Hypoxia-inducible TAp73 supports tumorigenesis by regulating the angiogenic transcriptome[J]. Nature cell biology, 2015.