Yoo YG, Kong G, Lee MO.. Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J 25: 1231-1241

Hanyang University, Sŏul, Seoul, South Korea
The EMBO Journal (Impact Factor: 10.43). 04/2006; 25(6):1231-41. DOI: 10.1038/sj.emboj.7601025
Source: PubMed


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-1alpha (HIF-1alpha), 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-1alpha protein were enhanced. MTA1 and HIF-1alpha are physically associated in vivo and they were localized completely in the nucleus when coexpressed. MTA1 induced the deacetylation of HIF-1alpha by increasing the expression of histone deacetylase 1 (HDAC1). MTA1 counteracted to the action of acetyltransferase, ARD1, and it did not stabilize the HIF-1alpha 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-1alpha 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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Available from: Mi-Ock Lee, Nov 24, 2014
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    • "Protein SSAT2 stabilizes the union between VHL-E3 ubiquitin ligase complex and HIF-1í µí»¼ promoting HIF-1í µí»¼ degradation [40]. HIF-1í µí»¼ can be acetylated in the Lys532 by ARD1 for its subsequent degradation via VHL [41], but the " metastasis-associated protein 1 " (MTA1) can counteract the activity of ARD1 [42]. " VHL-interacting deubiquitinating enzyme 2 " (VDU2) is another protein that stabilizes HIF-1í µí»¼, because it deubiquitinates HIF-1í µí»¼ avoiding its degradation [43] [44]. "
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