Wu J, Carmen A A, Kobayashi R, Suka N, Grunstein M
Department of Biological Chemistry, University of California School of Medicine and the Molecular Biology Institute, Boyer Hall, University of California, Los Angeles, CA 90095, USA.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4391-6. doi: 10.1073/pnas.081560698. Epub 2001 Apr 3.
Histone deacetylase HDA1, the prototype for the class II mammalian deacetylases, is likely the catalytic subunit of the HDA1-containing complex that is involved in TUP1-specific repression and global deacetylation in yeast. Although the class I RPD3-like enzymatic complexes have been well characterized, little is known about the identity and interactions of the factors that associate to form the HDA1 complex. In this paper, we identify related HDA2 and HDA3 proteins that are found in the HDA1 complex and show that HDA1 interacts with itself and with the HDA2-HDA3 subcomplex to form a likely tetramer. These interactions are necessary for catalytic activity because mutations in any of the three components disrupt activity both in vitro and in vivo. In this respect the HDA1 complex differs from yeast RPD3, which has components such as SIN3 that are not essential for activity in vitro, and yeast HOS3, which has intrinsic in vitro activity as a homodimer in the absence of other subunits.
组蛋白去乙酰化酶HDA1是II类哺乳动物去乙酰化酶的原型，它可能是含HDA1复合物的催化亚基，该复合物参与酵母中TUP1特异性抑制和全局去乙酰化。尽管I类RPD3样酶复合物已得到充分表征，但对于形成HDA1复合物的相关因子的身份和相互作用却知之甚少。在本文中，我们鉴定了在HDA1复合物中发现的相关HDA2和HDA3蛋白，并表明HDA1与自身以及HDA2 - HDA3亚复合物相互作用形成可能的四聚体。这些相互作用对于催化活性是必需的，因为三个组分中任何一个的突变都会破坏体外和体内的活性。在这方面，HDA1复合物不同于酵母RPD3，后者具有如SIN3等对体外活性非必需的组分，也不同于酵母HOS3，后者在没有其他亚基的情况下作为同二聚体具有内在的体外活性。
