Premium
Evidence for a p53‐independent pathway for upregulation of SDI1/CIP1/WAF1/P21 RNA in human cells
Author(s) -
Johnson Mac,
Dimitrov Diana,
Vojta Patrick J.,
Barrett J. Carl,
Noda Asao,
PereiraSmith Olivia M.,
Smith James R.
Publication year - 1994
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/mc.2940110202
Subject(s) - biology , cyclin dependent kinase , transactivation , downregulation and upregulation , gene , rna , gene expression , cdk inhibitor , dna synthesis , cell cycle , dna , messenger rna , microbiology and biotechnology , cancer research , genetics
SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening cDNAs prepared from senescent, terminally nondividing human cells. Other groups then cloned this gene as a cyclin‐dependent kinase (cdk)‐interacting protein (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes transactivated by p53 ( WAF1 ). p53 levels are low in senescent and quiescent contact‐inhibited or serum‐deprived normal human cells, which we have found express high levels of SDI1 mRNA. This indicates that alternate pathways for upregulation of message level of this gene may exist. We therefore proceeded with the study presented here, treating human cells with a variety of growth‐arrest‐inducing agents, including some that damaged DNA, and found that RNA levels of SDI1 were increased in all cases that resulted in growth inhibition. More important, with the exception of γ‐radiation, most of these agents were able to elevate SDI1 message levels in cells lacking wild‐type p53. At least two distinct kinetic profiles for RNA induction were observed, one that implicated p53 transactivation and occurred early enough to cause arrest, and another that clearly was p53 independent and suggested a role for the SDI1 gene product in the maintenance rather than in the cause of inhibition of DNA synthesis. ©1994 Wiley‐Liss, Inc.