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PMID: 7883998 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Posttranscriptional stabilization underlies p53-independent induction of p21WAF1/CIP1/SDI1 in differentiating human leukemic cells.

The Journal of clinical investigation ·Vol. 95 ·No. 3 ·1995-03-00 ·Pages 973-9

Schwaller J, Koeffler HP, Niklaus G, Loetscher P, Nagel S, Fey MF, Tobler A

Abstract

p21WAF/CIP1/SDI1 is a recently identified gene expressed in cells harboring wild-type but not mutant p53 gene. It encodes a nuclear protein of 21 kD which inhibits cyclin-dependent kinase activity. Constitutive p21WAF1/CIP1/SDI1 mRNA expression was detected in neoplastic cells from patients with various hematological malignancies as well as in normal bone marrow mononuclear cells and in myeloid and lymphoid cell lines independent of their p53 status. Induced differentiation of the p53-deficient promyelocytic HL-60 cells along the monocytic lineage by phorbol ester or 1a,25 dihydroxyvitamin D3 resulted in a marked increase of both p21WAF1/CIP1/SDI1 mRNA and protein expression due to enhanced mRNA stability. Differentiation towards the granulocytic lineage by all-trans retinoic acid or dimethylsulfoxide failed to produce this effect. p21WAF1/CIP1/SDI1 is an immediate early gene since its upregulation occurred independently of de novo protein synthesis. The induction of p21WAF1/CIP1/SDI1 expression and its regulation in p53-deficient differentiating leukemic cells support the idea of an additional, p53-independent role of p21WAF1/CIP1/SDI1 in human hematopoiesis.

MeSH Terms
Cyclin-Dependent Kinase Inhibitor p21 Cyclins/biosynthesis,genetics Dimethyl Sulfoxide/pharmacology Gene Expression Regulation, Neoplastic Granulocytes/physiology Humans Leukemia/genetics Monocytes/physiology RNA, Messenger/metabolism Tetradecanoylphorbol Acetate/pharmacology Transcription, Genetic Tretinoin/pharmacology Tumor Cells, Cultured/drug effects Tumor Suppressor Protein p53/genetics
Chemicals
CDKN1A protein, human Cyclin-Dependent Kinase Inhibitor p21 Cyclins RNA, Messenger Tumor Suppressor Protein p53 Tretinoin Tetradecanoylphorbol Acetate Dimethyl Sulfoxide
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Schwaller J
Laboratory for Clinical and Experimental Research, University of Berne, Switzerland.
Koeffler H P
Niklaus G
Loetscher P
Nagel S
Fey M F
Tobler A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117806
Published
1995-03-00
Pages
973-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC441429
Subset
IM
Grants
NCI NIH HHS · CA-26038 · United States
NIDDK NIH HHS · DK-42792 · United States
External Links
PubMed source DOI: 10.1172/JCI117806 PMC Full Text View journal details
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