Identification of a novel p53 functional domain that is necessary for mediating apoptosis

Jianhui Zhu, Wenjing Zhou, Jieyuan Jiang, Xinbin Chen

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145 Citations (Scopus)

Abstract

The ability of p53 to induce apoptosis requires its sequence-specific DNA binding activity; however, the transactivation-deficient p53(Gln22- Ser23) can still induce apoptosis. Previously, we have shown that the region between residues 23 and 97 in p53 is necessary for such activity. In an effort to more precisely map a domain necessary for apoptosis within the N terminus, we found that deletion of the N-terminal 23 amino acids compromises, but does not abolish, p53 induction of apoptosis. Surprisingly, p53(Δ1-42), which lacks the N-terminal 42 amino acids and the previously defined activation domain, retains the ability to induce apoptosis to an even higher level than wild-type p53. A more extensive deletion, which eliminates the N-terminal 63 amino acids, renders p53 completely inert in mediating apoptosis. In addition, we found that both p53(Δ1-42) and p53(Gln22- Ser23) can activate a subset of cellular p53 targets. Furthermore, we showed that residues 53 and 54 are critical for the apoptotic and transcriptional activities of both p53(Δ1-42) and p53(Gln22-Ser23). Taken together, these data suggest that within residues 43-63 lie an apoptotic domain as well as another transcriptional activation domain. We therefore postulate that the apoptotic activity in p53(Gln22-Ser23) and p53(Δ1-42) is still transcription-dependent.

Original languageEnglish (US)
Pages (from-to)13030-13036
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number21
DOIs
StatePublished - May 22 1998
Externally publishedYes

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Apoptosis
Amino Acids
Transcriptional Activation
Chemical activation
Transcription
DNA

ASJC Scopus subject areas

  • Biochemistry

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Identification of a novel p53 functional domain that is necessary for mediating apoptosis. / Zhu, Jianhui; Zhou, Wenjing; Jiang, Jieyuan; Chen, Xinbin.

In: Journal of Biological Chemistry, Vol. 273, No. 21, 22.05.1998, p. 13030-13036.

Research output: Contribution to journalArticle

Zhu, Jianhui ; Zhou, Wenjing ; Jiang, Jieyuan ; Chen, Xinbin. / Identification of a novel p53 functional domain that is necessary for mediating apoptosis. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 21. pp. 13030-13036.
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