Journal Article

AMPK-β1 subunit is a p53-independent stress responsive protein that inhibits tumor cell growth upon forced expression

Jun Li, Ping Jiang, Megan Robinson, Theodore S. Lawrence and Yi Sun

in Carcinogenesis

Volume 24, issue 5, pages 827-834
Published in print May 2003 | ISSN: 0143-3334
Published online May 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg032
AMPK-β1 subunit is a p53-independent stress responsive protein that inhibits tumor cell growth upon forced expression

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In an effort to search for genes responsible for cell growth arrest and/or apoptosis associated with p53 signaling pathways, we profiled a human lung carcinoma line H1299, expressing a temperature-sensitive p53 (V138) against Affymetric human U95Av2 GeneChip A, consisting of 12 000 genes. 133 genes were identified that were either induced or repressed in response to p53-dependent cell growth arrest and apoptotic conditions. Among them, the β1 subunit, but not other subunits of the AMP-activated protein kinase (AMPK) was strongly induced. The p53 consensus binding site search in the AMPK-β1 promoter and the first intron identified four such putative sites. However, p53 failed to bind to any of these sites as assayed by in vitro gel retardation and in vivo chromatin immunoprecipitation. Furthermore, northern analysis showed that induction of this gene is independent of p53, as increased expression of the gene was observed in p53 null H1299/Neo control cells when the temperature was shifted to 32°C. Moreover, a DNA damaging agent, etoposide, also induced β1 subunit expression in multiple human tumor cells, regardless of p53 status. Thus, the β1 subunit of AMPK is not a p53 downstream target gene, but can be induced by cold shock or the chemotherapeutic drug, etoposide in a p53-independent manner. To determine the biological significance of AMPK-β1 induction, we over-expressed the gene in two tumor cell lines, H1299 and U2-OS. In both lines, forced AMPK-β1 expression inhibits tumor cell growth, suggesting that AMPK-β1 induction may facilitate stress-induced growth inhibition and cell killing.

Keywords: AMPK, AMP-activated protein kinase.

Journal Article.  5671 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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