Δ160p53 is a novel N‐terminal p53 isoform encoded by Δ133p53 transcript

Marcel, Virginie; Perrier, Stéphane; Aoubala, Mustapha; Ageorges, Sylvain; Groves, Michael J.; Diot, Alexandra; Fernandes, Kenneth; Tauro, Sudhir; Bourdon, Jean-Christophe

doi:10.1016/j.febslet.2010.10.005

Cited by 111 publications

(116 citation statements)

References 13 publications

(39 reference statements)

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“…The lower band detected below the Δ133p53 proteins corresponds to an alternative initiation of translation from a downstream methionine (residue 160). 13 The degradation of the Δ160p53 forms was concomitant with the degradation of their Δ133p53 counterparts.…”

Section: Resultsmentioning

confidence: 99%

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The p53 isoforms are differentially modified by Mdm2

et al. 2012

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Section: Resultsmentioning

confidence: 99%

“…1A). 7,13 These isoforms have been shown to be expressed at the mRNA level, to varying degrees, in a number of different normal and tumor tissues. 11,12 p53β and Δ133p53 proteins have been shown to have important functions in regulating cell senescence and apoptosis.…”

Section: The P53 Isoforms Are Differentially Modified By Mdm2mentioning

confidence: 99%

The p53 isoforms are differentially modified by Mdm2

et al. 2012

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“…Human TP53 encodes 12 isoforms due to the presence of multiple promoters, translation initiation sites and alternative sites of splicing (Bourdon et al, 2005;Marcel et al, 2010a). These isoforms are expressed in normal tissues in a tissue-specific manner, and at least some of them appear to participate in the regulation of full length-p53 (FL-p53) and to play a role in tumor progression (Bourdon, 2007).…”

Section: Future Perspectives : the Importance Of P53 Isoformsmentioning

confidence: 99%

“…133p53 is absent in normal mammary tissues, but present in breast cancers, and its overexpression is correlated with the progression of colon cancer from adenomas to carcinomas. The 160p53 isoform results from an alternative translation intiation site, within the same mRNA transcript that encodes 133p53 (Marcel et al, 2010a). The function of this isoform, identified very recently, is presently unknown.…”

Section: Future Perspectives : the Importance Of P53 Isoformsmentioning

confidence: 99%

p53: Point Mutations, SNPs and Cancer

Fang¹,

Simeonova²,

Toledo³

2012

Point Mutation

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“…Those transcripts generate two different N-terminal p53 isoforms, D133p53 and D160p53, through the use of two alternative translational initiation sites (codons 133 or 160). 18 D133p53a inhibits replicative senescence, p53-mediated apoptosis and G1 arrest in response to stress, without inhibiting p53-mediated G2 cell cycle arrest. 16,19 Thus, D133p53a isoform is a strong modulator of p53-suppressive functions and presents similar characteristics to DNp63 and DNp73 towards their full-length form.…”

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Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity

et al. 2011

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In response to stress, p53 binds and transactivates the internal TP53 promoter, thus regulating the expression of its own isoform, D133p53a. Here, we report that, in addition to p53, at least four p63/p73 isoforms regulate D133p53 expression at transcriptional level: p63b, DNp63a, DNp63b and DNp73c. This regulation occurs through direct DNA-binding to the internal TP53 promoter as demonstrated by chromatin immunoprecipitation and the use of DNA-binding mutant p63. The promoter regions involved in the p63/p73-mediated transactivation were identified using deleted, mutant and polymorphic luciferase reporter constructs. In addition, we observed that transient expression of p53 family members modulates endogenous D133p53a expression at both mRNA and protein levels. We also report concomitant variation of p63 and D133p53 expression during keratinocyte differentiation of HaCat cells and induced pluripotent stem cells derived from mutated p63 ectodermal dysplasia patients. Finally, proliferation assays indicated that D133p53a isoform regulates the anti-proliferative activities of p63b, DNp63a, DNp63b and DNp73c. Overall, this study shows a strong interplay between p53, p63 and p73 isoforms to orchestrate cell fate outcome. The TP53 family, composed of TP53, TP63 and TP73 genes, presents a strong homology of structures and expression patterns. 1,2 The three genes encode several protein isoforms carrying distinct N-termini (TA or D forms) and C-termini (a, b, g, y), because of the use of alternative promoters, splicing sites and translational initiation sites. 3,4 The full-length proteins also share a similar protein structure with a N-terminal transactivation domain, a central DNA-binding domain (DBD) and a C-terminal oligomerisation domain. 4,5 A strong interplay has been described between p53 family members. They all bind specifically to DNA response elements (p53RE), modulate gene expression and thus cellfate outcome. 6 Moreover, the p53-mediated apoptosis is severely impaired in the absence of p63 and p73 in response to DNA damage. 7 The interplay between p53 family members is not limited to transcriptional modulation of common target genes; they also regulate each other's expression and activity. 6 p53, p73 and DNp73 transactivate the promoter of DNp73 isoform, which in turn, inhibits the p53-and p73-mediated transcriptional activity and apoptosis through direct competition for DNAbinding. [8][9][10][11][12] Similarly, p53, DNp63 and p73g modulate the activity of the internal TP63 promoter regulating DNp63 expression, which inhibits p53, p63 and p73 transcriptional activities. 2,6,[13][14][15] Recently, it has been reported that p53 regulates the transcription of D133p53 isoform, which lacks the entire transactivation domain and part of the DBD. 16,17 p53 directly binds to p53REs located within the internal TP53 promoter leading to an increase of D133p53 mRNAs. Those transcripts generate two different N-terminal p53 isoforms, D133p53 and D160p53, through the use of two alternative translational initiation sites (co...

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Δ160p53 is a novel N‐terminal p53 isoform encoded by Δ133p53 transcript

Cited by 111 publications

References 13 publications

The p53 isoforms are differentially modified by Mdm2

The p53 isoforms are differentially modified by Mdm2

p53: Point Mutations, SNPs and Cancer

Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity

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