Premium
Gadd45α does not modulate the carboplatin or 5‐fluorouracil‐induced apoptosis in human papillomavirus‐positive cells
Author(s) -
Singh Sandeep,
Upadhyay Ankur Kumar,
Ajay Amrendra Kumar,
Bhat Manoj Kumar
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21111
Subject(s) - gadd45 , apoptosis , transfection , downregulation and upregulation , microbiology and biotechnology , poly adp ribose polymerase , western blot , biology , dna damage , cancer research , chemistry , cell culture , cell cycle checkpoint , polymerase , cell cycle , gene , dna , biochemistry , genetics
Gadd45α is shown to be induced by a wide spectrum of DNA‐damaging agents and implicated in negative regulation of cell growth by causing G2‐M arrest or induction of apoptosis. In the present study, we explored the involvement of p53 in the promoter activation of Gadd45α as well as the role of Gadd45α in carboplatin (Carb) or 5‐fluorouracil (5‐FU)‐induced apoptosis in human papillomavirus virus (HPV)‐positive HEp‐2 and HeLa cells. We report that Carb or 5‐FU upregulate Gadd45α and p53 in both these cells. Transient transfection of chloramphenicol acetyl transferase (CAT)‐reporter construct driven by Gadd45α promoter clearly indicated that Gadd45α upregulation was mediated through activation of its promoter. Inhibition of p53 function by dominant‐negative‐p53 expression partially suppressed the activation of Gadd45α promoter. Further, the induction of apoptosis was assessed by detection of poly (ADP‐ribose) polymerase (PARP) cleavage by Western blot analysis. Inhibition of upregulated Gadd45α expression by antisense expression vector did not modulate the Carb or 5‐FU‐induced apoptosis. Overall, we conclude that Gadd45α promoter activation partially depends on p53 function in HPV‐positive cells. Moreover, Gadd45α protein does not modulate Carb or 5‐FU‐induced apoptosis in these cells. J. Cell. Biochem. 100: 1191–1199, 2007. © 2006 Wiley‐Liss, Inc.