The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase.
The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase.
复制标题
DOI：
10.1083/jcb.200205057
复制
发表时间：
2002-08-19
期刊：
影响因子：
--
通讯作者：
Verdin E
中科院分区：
文献类型：
--
作者：
Schwer B;North BJ;Frye RA;Ott M;Verdin E
酵母沉默信息调节因子（Sir）2蛋白通过其烟酰胺腺嘌呤二核苷酸（NAD）依赖性组蛋白去乙酰化酶活性将细胞代谢和转录沉默联系起来。我们报告，从哺乳动物细胞的线粒体含有固有的NAD依赖性脱乙酰酶活性。这种活性被NAD水解产物烟酰胺抑制，但不被抑制素A抑制，与III类脱乙酰酶一致。我们确定这种脱乙酰酶作为核编码的人类Sir2同源hSIRT3，并表明hSIRT3位于线粒体基质内。hSIRT3的线粒体输入依赖于富含碱性残基的NH2-末端两亲性α-螺旋。hSIRT3在线粒体基质中被蛋白水解加工成28-kD产物。这种加工可以用重组线粒体基质加工肽酶（MPP）在体外重建，并被突变的丝氨酸99和100抑制。hSIRT3的未加工形式是酶失活的，并且在体外被MPP切割后变得完全活化。这些观察结果表明存在潜在的III类脱乙酰酶，其在输入到人线粒体中时被催化活化。
The yeast silent information regulator (Sir)2 protein links cellular metabolism and transcriptional silencing through its nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase activity. We report that mitochondria from mammalian cells contain intrinsic NAD-dependent deacetylase activity. This activity is inhibited by the NAD hydrolysis product nicotinamide, but not by trichostatin A, consistent with a class III deacetylase. We identify this deacetylase as the nuclear-encoded human Sir2 homologue hSIRT3, and show that hSIRT3 is located within the mitochondrial matrix. Mitochondrial import of hSIRT3 is dependent on an NH2-terminal amphipathic α-helix rich in basic residues. hSIRT3 is proteolytically processed in the mitochondrial matrix to a 28-kD product. This processing can be reconstituted in vitro with recombinant mitochondrial matrix processing peptidase (MPP) and is inhibited by mutation of arginines 99 and 100. The unprocessed form of hSIRT3 is enzymatically inactive and becomes fully activated in vitro after cleavage by MPP. These observations demonstrate the existence of a latent class III deacetylase that becomes catalytically activated upon import into the human mitochondria.
登录
查看更多内容
DOI：
10.1083/jcb.93.1.97
发表时间：
1982-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujiki Y;Hubbard AL;Fowler S;Lazarow PB
通讯作者：
Lazarow PB
影响因子：
3.5
作者：
Devin, A;Guerin, B;Rigoulet, M
通讯作者：
Rigoulet, M
影响因子：
64.8
作者：
Finnin, MS;Donigian, JR;Pavletich, NP
通讯作者：
Pavletich, NP
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA
DOI：
10.1093/protein/4.1.33
发表时间：
1990-10-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
GAVEL, Y;VONHEIJNE, G
通讯作者：
VONHEIJNE, G