Fig. 3. Proposed mechanism for transcription-dependent p73-induced apoptosis. In response to cellular stress, the pro-apoptotic, transcriptionally active p73 (TAp73) isoform transactivates pro-apoptotic genes such as Bax and GRAMD4 and apoptin, whereas the anti-apoptotic transcriptionally inactive p73 (DNp73) isoform inhibits the pro-apoptotic activity of TAp73. In turn, overexpressed pro-apoptotic proteins act directly on the mitochondria to trigger apoptosis. For the extrinsic apoptotic pathway, apoptosis is initiated upon binding of CD95-L to the CD95 death receptor, induced by p73. The apoptotic activity of nuclear p73 is indirect via these mechanisms. Dotted arrows indicate the activation pathway for the viral protein apoptin and the solid arrows designate the pathways for other human proteins.
