DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes

Costanzo, Antonio; Merlo, Paola; Pediconi, Natalia; Fulco, Marcella; Sartorelli, Vittorio; Cole, Philip A.; Fontemaggi, Giulia; Fanciulli, Maurizio; Schiltz, Louis; Blandino, Giovanni; Balsano, Clara; Levrero, Massimo

doi:10.1016/s1097-2765(02)00431-8

Cited by 301 publications

(277 citation statements)

References 35 publications

Supporting

Mentioning

260

Contrasting

Unclassified

Order By: Relevance

“…68 Furthermore, these events have been linked to the induction of proapoptotic target genes. 69 Understanding how Pin1-induced conformational shifts affect the interaction of p53 with some of its partners and modulating its functions, may help us explain the specificity of the p53 response.…”

Section: The Prolyl Isomerase Pin1mentioning

confidence: 99%

Some p53-binding proteins that can function as arbiters of life and death

2006

View full text Add to dashboard Cite

Four sets of p53-binding proteins are discussed in this review. These are the E2F family, the ASPP family, Y-boxbinding protein YB1, and the prolyl isomerase Pin1. Each appears to play a role in the decision by p53 to induce an arrest of cell proliferation or apoptosis and they may also be independent markers of cancer. Their activities appear to be linked with the cell cycle and they may also interact with each other. In this review, the properties of each protein class are discussed as well as how they affect p53 functions. A model is proposed as to how their activities might be coordinated.

show abstract

Section: The Prolyl Isomerase Pin1mentioning

confidence: 99%

Some p53-binding proteins that can function as arbiters of life and death

2006

View full text Add to dashboard Cite

show abstract

“…The transcriptional activity of p53 family members is mainly regulated at the posttranslational level. Indeed, phosphorylation, acetylation, prolyl-isomerization and sumoylation are the most characterized post-translation modifications of p53 family members that impact on their transcriptional activity either by potentiating or dictating the selectivity in the activation of the proper target gene (Jayaraman and Prives, 1999;Costanzo et al, 2002;Brooks and Gu, 2003;Xu, 2003;Bode and Dong, 2004;Strano et al, 2005). The net result of this selective transcriptional activation is the maximization of the efficacy of the anti-tumoral effects.…”

Section: Introductionmentioning

confidence: 99%

Mutant p53: an oncogenic transcription factor

Strano¹,

Dell’Orso²,

Agostino³

et al. 2007

Oncogene

246

184

View full text Add to dashboard Cite

Inactivation of tumor-suppressor genes is one of the key hallmarks of a tumor. Unlike other tumor-suppressor genes, p53 is inactivated by missense mutations in half of all human cancers. It has become increasingly clear that the resulting mutant p53 proteins do not represent only the mere loss of wild-type p53 tumor suppressor activity, but gain new oncogenic properties favoring the insurgence, the maintenance, the spreading and the chemoresistance of malignant tumors. The actual challenge is the fine deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. In this review, we will focus mainly on the transcriptional activity of mutant p53 proteins as one of the potential molecular mechanisms. To date, the related knowledge is still quite scarce and many of the raised questions of this review are yet unanswered.

show abstract

“…After DNA damage, TAp73 rapidly accumulates (Agami et al, 1999;Gong et al, 1999) predominantly via transcription-independent mechanisms. 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).…”

Section: Introductionmentioning

confidence: 99%

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

Sayan

Gogvadze

et al. 2008

Oncogene

View full text Add to dashboard Cite

The p73 protein, a member of the p53 family, has both developmental and tumorigenic functions. Here we show that p73 is cleaved by caspase-3 and -8 both in vitro and in vivo during apoptosis elicited by DNA-damaging drugs and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor ligation. TAp73 and some of its cleavage products are localized to mitochondria. siRNA-mediated downregulation of p73 expression induced a small but significant change in the susceptibility of HCT116 cells to TRAIL-induced apoptosis. A transcription-deficient mutant of TAp73 enhanced TRAIL-induced apoptosis suggesting that p73 protein has transcriptionindependent functions during death receptor-mediated apoptosis. Additionally, recombinant p73 protein induced cytochrome c release from isolated mitochondria providing evidence that nonnuclear p73 may have additional functions in the progression of apoptosis.

show abstract

DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes

Cited by 301 publications

References 35 publications

Some p53-binding proteins that can function as arbiters of life and death

Some p53-binding proteins that can function as arbiters of life and death

Mutant p53: an oncogenic transcription factor

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

Contact Info

Product

Resources

About