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| Subject Categories: Signal Transduction | Molecular Biology of Disease |
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| The EMBO Journal
(2006) 25, 1231–1241, doi:10.1038/sj.emboj.7601025 Published online 2 March 2006 |
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Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1 protein by recruiting histone deacetylase 1 |
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| Young-Gun Yoo1, Gu Kong2 and Mi-Ock Lee1 |
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1 College of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul, Korea 2 Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea To whom correspondence should be addressed Mi-Ock Lee, College of Pharmacy and Bio-MAX Institute, Seoul National University, Seoul 151-742, Korea. Tel.: +82 2 880 9331; Fax: +82 2 872 1795; E-mail: molee@snu.ac.kr Received 11 October 2005; Accepted 6 February 2006; Published online 2 March 2006. |
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| Abstract |
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| The expression of metastasis-associated protein 1 (MTA1) correlates well with tumor metastases; however, the associated molecular mechanism is not fully understood. Here, we explored the possibility of cross-talk between MTA1 and hypoxia-inducible factor-1 (HIF-1), a key regulator of angiogenic factors. We observed that the expression of MTA1 was strongly induced under hypoxia in breast cancer cell lines such as MCF-7 and MDA-MB-231. When MTA1 was overexpressed, the transcriptional activity and stability of HIF-1 protein were enhanced. MTA1 and HIF-1 are physically associated in vivo and they were localized completely in the nucleus when coexpressed. MTA1 induced the deacetylation of HIF-1 by increasing the expression of histone deacetylase 1 (HDAC1). MTA1 counteracted to the action of acetyltransferase, ARD1, and it did not stabilize the HIF-1 mutant that lacks the acetylation site, K532R. These results indicate that acetylation is the major target of MTA1/HDAC1 function. Collectively, our data provide evidence of a positive cross-talk between HIF-1 and MTA1, which is mediated by HDAC1 recruitment, and indicate a close connection between MTA1-associated metastasis and HIF-1-induced tumor angiogenesis. |
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| Keywords: HDAC1, HIF-1, hypoxia, metastasis, MTA1 |
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