p73: Friend or foe in tumorigenesis

ΔNp73 stabilises TAp73 proteins but compromises their function due to inhibitory hetero-oligomer formation

“…1 This predicts functional similarities for the regulation of cell cycle and apoptosis. Indeed, TAp73 becomes transcriptionally activated upon DNA-damaging agents and oncogenes independent of p53 1,2 and ectopic TAp73 transactivates many p53 target genes involved in cell cycle arrest and apoptosis.…”

“…Indeed, TAp73 becomes transcriptionally activated upon DNA-damaging agents and oncogenes independent of p53 1,2 and ectopic TAp73 transactivates many p53 target genes involved in cell cycle arrest and apoptosis. 1 Also, intact TAp73 function is an important determinant of cellular sensitivity to anticancer agents. 3 However, the roles of TP53 and TP73 in mammalian tumorigenesis seem to be fundamentally different.…”

“…In contrast to TP53, TP73 is almost never targeted by inactivating mutations in human tumors. 1 To the contrary, many different types of cancers overexpress TP73 (reviewed in Moll et al 4 ). Moreover, TP73 knockout mice lack a cancer phenotype but exhibit a developmental phenotype.…”

p73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis

“…Indeed, the major determinants regulating p73 accumulation are tyrosine phosphorylation by c-abl, acetylation by p300 and Itch downregulation (Costanzo et al, 2002;Bernassola et al, 2004;Mantovani et al, 2004;Rossi et al, 2005). Once accumulated, TAp73 transactivates genes like p21, Bax and Puma to induce cell cycle arrest or apoptosis (see Melino et al, 2002 for a review).…”

Apoptosis and disease: a matter of cell fate

“…These results led Melino to propose that the ratio of TAp73 to DNp73 may dictate the response to chemotherapy and suggest that TAp73 is the oncologist's friend, whereas DNp73 may prove to be the foe in tumorigenesis. 11 Orchestration of cell death: a tale of death receptors and mitochondria Apoptosis can be induced either by activation of death receptors or by perturbation of mitochondria [12][13][14] (Figure 2). G Cohen (Leicester, UK) explained how the mitochondrial pathway can be engaged in response to death receptor signalling, facilitating apoptosis by release from the mitochondria of cytochrome c or the inhibitor of apoptosis (IAP) antagonists Smac/Diablo and Omi/HtrA2.…”