Premium
Modulation of p53 protein conformation and DNA‐binding activity by intracellular chelation of zinc
Author(s) -
Verhaegh Gerald W.,
Parat MarieOdile,
Richard MarieJeanne,
Hainaut Pierre
Publication year - 1998
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199803)21:3<205::aid-mc8>3.0.co;2-k
Subject(s) - biology , intracellular , dna , mutant , ethylenediamine , chelation , microbiology and biotechnology , zinc , biochemistry , gene , chemistry , inorganic chemistry , organic chemistry
The transcription factor p53 controls the proliferation and survival of cells exposed to DNA damage. The specific DNA‐binding domain of p53 (residues 102–292) has a complex tertiary structure that is stabilized by zinc. In this study, we showed that exposure of cultured cells to the membrane‐permeable chelator N,N,N′, N′‐tetrakis(2‐ pyridylmethyl)ethylenediamine induced wild‐type p53 to accumulate in an immunologically “mutant” form (Pab240+, Pab1620–) with decreased DNA‐binding activity. Removal of N,N,N′,N′‐tetrakis(2‐pyridylmethyl)ethylenediamine from culture medium allowed p53 to refold into the immunologically wild‐type form, followed by a transient increase in DNA binding, expression of the cyclin‐dependent kinase inhibitor p21 WAF1 , and cell‐cycle delay in the G 1 phase. Thus, modulation of intracellular zinc induced conformational changes in p53 that activated wild‐type function, suggesting that metalloregulation may play a role in controlling p53. Mol. Carcinog. 21:205–214, 1998. © 1998 Wiley‐Liss, Inc.