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ZBTB5 is a potential tumor suppressor in the absence of functional p53
Author(s) -
Koh DongIn,
Hur ManWook
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.678.11
Subject(s) - zinc finger , repressor , biology , suppressor , transcription (linguistics) , cell cycle , transcription factor , tumor suppressor gene , e2f1 , oncogene , cell growth , microbiology and biotechnology , gene , cancer research , carcinogenesis , genetics , linguistics , philosophy
Previously, we isolated and characterized a novel POZ domain Krüppel like zinc finger transcription repressor, ZBTB5 (Zinc finger and BTB domain containing 5). SAGE analysis showed that ZBTB5 expression is higher in retinoblastoma and muscle cancer tissues. Our data suggested that ZBTB5 is a potent transcription repressor of cell cycle arrest gene p21 and a potential proto‐oncogene stimulating cell proliferation. Interestingly, in the HCT116 p53 null cells lacking functional tumor suppressor p53, expression of ZBTB5 was greatly induced prior to induction of cell cycle arrest gene p21 when cells were expose to DNA damaging agent, etoposide. ZBTB5 potently activated transcription of p21 gene in the absence of p53. ZBTB5 and Sp1 synergistically activates transcription by acting on the p21 promoter lacking distal p53 binding elements both in the p53 null and p53 positive cells. Furthermore, ZBTB5 increased transcription of p21 in the presence of dominant negative mutant form of p53. Our data suggest that ZBTB5 has functional duality in the regulation of cell proliferation and can acts either as oncogene or tumor suppressor depending on presence or absence of functional p53.