TP73, as a TP53 homologue, drew the attention of tumor biologists because it is rarely mutated in human cancers and can induce cell cycle arrest and apoptosis by activating genes also regulated by p53. However, TP73 harbors an additional promoter that produces a dominant negative p73 protein (Delta Np73) having the opposite effect of the TAp73 protein. Thus, the regulation F of p53 responsive genes in the absence of p53 relies on a critical balance I between different p73 gene-derived proteins. Recent reports have described additional complexity in the mechanism of action of transcriptionally active p73 (TAp73) in the induction of cell death. The molecular mechanism through which p73 induces apoptosis involves (i) expression and changes in subcellular localization of scotin, producing an endoplasmic reticulum (ER) stress; and (ii) transactivation of PUMA and Bax, thus determining cell fate. On the contrary, Delta Np73 inhibits apoptosis, thus contributing to the oncogenic potential of neuroblastoma cells.
Rossi, M., Sayan, A.e., Terrinoni, A., Melino, G., Knight, R.a. (2004). Mechanism of induction of apoptosis by p73 and its relevance to neuroblastoma biology. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1028(1), 143-149 [10.1196/annals.1322.015].
Mechanism of induction of apoptosis by p73 and its relevance to neuroblastoma biology
Terrinoni A.;Melino G.;
2004-01-01
Abstract
TP73, as a TP53 homologue, drew the attention of tumor biologists because it is rarely mutated in human cancers and can induce cell cycle arrest and apoptosis by activating genes also regulated by p53. However, TP73 harbors an additional promoter that produces a dominant negative p73 protein (Delta Np73) having the opposite effect of the TAp73 protein. Thus, the regulation F of p53 responsive genes in the absence of p53 relies on a critical balance I between different p73 gene-derived proteins. Recent reports have described additional complexity in the mechanism of action of transcriptionally active p73 (TAp73) in the induction of cell death. The molecular mechanism through which p73 induces apoptosis involves (i) expression and changes in subcellular localization of scotin, producing an endoplasmic reticulum (ER) stress; and (ii) transactivation of PUMA and Bax, thus determining cell fate. On the contrary, Delta Np73 inhibits apoptosis, thus contributing to the oncogenic potential of neuroblastoma cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
