Hypoxia is the status of low oxygen level or insufficient supply of oxygen to tissues. Under hypoxic condition, BNIP3, a member of the BH3-only protein family, is transcriptionally induced by HIF-1a, and causes cell death/apoptosis. This process plays a role in ischemic heart disease, cerebral stroke and tumor progression.  

Abundant evidence indicates that p53 functions as a tumor suppressor through its ability to induce apoptosis in cells under stressful conditions. However, there are disagreements regarding p53’s function in hypoxia induced cell death/apoptosis. Recently, Dr. FENG Xi and LIU Xing from the Research Group of Molecular Toxicology (Principal Investigator: Prof. XIAO Wuhan) at Institute of Hydrobiology, Chinese Academy of Sciences (IHB) firstly find that p53 can suppress the expression of BNIP3 under both normaxic and hypoxic conditions.  

Through promoter analysis, Northern blot, semi-q RT-PCR and Western Blot, they present evidence that p53 protein can directly bind to p53 RE motif on BNIP3 promoter, recruit mSin3a co-repressor, repress the expression of BNIP3 and inhibit hypoxia-induced cell death/apoptosis mediated by BNIP3. Further investigation using zebrafish as in vivo model shows that nip3a, the zebrafish BNIP3 homologue, can also response to hypoxia’s inducing and p53’s repression. Exposure to hypoxia causes dramatic apoptosis in 2dpf embryos and the numbers of apoptotic cells are higher in p53 mutants and p53 morphants, which can be rescued by overexpression of p53 or a dominant negative form of the nip3a lacking the c-terminal TM domain.  

The results suggest a novel function of p53 in hypoxia-induced cell death and may contribute to a more complete understanding of the molecular mechanism underlying p53’s activity in hypoxia-induced apoptosis. 

This research has been published online in EMBO Journal on July 26. The work was supported by Major State Basic Research Development Program (973), National Natural Science Foundation and Science Foundation of the Chinese Academy of Sciences. 

Related link: http://www.nature.com/emboj/journal/vaop/ncurrent/pdf/emboj2011248a.pdf