Figure 5.

Illustrative diagrams of PUMA (BBC3) isoforms and activity. (A) PUMA is an essential inducer of p53-dependent and independent apoptosis. The tumor suppressor p53 can lead to cell cycle arrest or apoptosis depending on subcellular context and cell type. PUMA is needed for p53- dependent apoptosis mediated by hypoxia, DNA damage, proteasome inhibitors and genotoxic stress. Apoptosis is also induced by PUMA via p53-independent mechanism mediated by ischemia/reperfusion, kinase inhibitors, glucocorticoids and cytokine withdrawal (Reviewed in [71]); and (B) Alternative splicing of PUMA pre-mRNA yields mRNA PUMA α, β, δ and γ splice variants [20]. PUMA-α and -β splice variants contain BH3 domain, while PUMA-γ and δ have no BH3 domain. Thus BH3 domain in PUMA-α and -β variants plays an important role in the induction of apoptosis [20] and this may reveal that abnormalities in splicing of PUMA transcripts may result in either an increase or decrease in apoptosis due to exclusion or inclusion of BH3 domain in its splice variants.