PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skeletal-muscle-specific calpain, CAPN3, scaffolds a CAPN3 substrate, CTBP1.
PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skeletal-muscle-specific calpain, CAPN3, scaffolds a CAPN3 substrate, CTBP1.
复制标题
PLEIAD/SIMC1/C5ORF25，一种用于骨骼肌肉特异性钙蛋白酶CAPN3的新型自动分解调节剂，CAPN3，CAPN3底物CTBP1。
DOI：
10.1016/j.jmb.2013.05.009
复制
发表时间：
2013-08-23
影响因子：
5.6
通讯作者：
Sorimachi H
中科院分区：
文献类型：
--
作者：
Ono Y;Iemura S;Novak SM;Doi N;Kitamura F;Natsume T;Gregorio CC;Sorimachi H
CAPN 3/p94/calpain-3是calpain蛋白酶家族的一个重要成员。已经报道了CAPN 3的多种肌细胞功能，并且该蛋白酶的突变导致肢带型肌营养不良症2A型。关于使CAPN 3如此多功能的分子机制知之甚少。一种假设是，CAPN 3的非常快速和彻底的自溶活性需要通过动态分子相互作用抑制特定的时间段。先前鉴定的CAPN 3和连接蛋白/肌联蛋白（肌肉肌节中的巨大分子）之间的相互作用支持这一假设;然而，非肌节相关CAPN 3的调控机制尚不清楚。在这里，我们报告了一种新的CAPN 3结合蛋白，PLEIAD [抑制自溶降解的平台元件;最初称为SIMC 1/C5 orf 25（含蛋白1/染色体5开放阅读框25的SUMO相互作用基序）]，抑制CAPN 3的蛋白酶活性。数据库分析表明，PLEIAD同源物，如CAPN 3同源物，在脊椎动物中进化保守。此外，我们发现PLEIAD还与CTBP 1（C-末端结合蛋白1）（一种转录辅助调节因子）相互作用，CTBP 1在表达CAPN 3的COS 7细胞中被蛋白水解。CTBP 1中鉴定的切割位点表明，它在被CAPN 3以及常规钙蛋白酶蛋白水解后经历功能修饰。这些结果表明，PLEIAD可以将其主要功能从CAPN 3抑制转移到CAPN 3底物募集，这取决于细胞环境。总之，我们的数据表明PLEIAD是CAPN 3的一种新型调控支架，正如其名称所反映的那样。
CAPN3/p94/calpain-3 is a skeletal-muscle-specific member of the calpain protease family. Multiple muscle cell functions have been reported for CAPN3, and mutations in this protease cause limb-girdle muscular dystrophy type 2A. Little is known about the molecular mechanisms that allow CAPN3 to be so multifunctional. One hypothesis is that the very rapid and exhaustive autolytic activity of CAPN3 needs to be suppressed by dynamic molecular interactions for specific periods of time. The previously identified interaction between CAPN3 and connectin/titin, a giant molecule in muscle sarcomeres, supports this assumption; however, the regulatory mechanisms of non-sarcomere-associated CAPN3 are unknown. Here, we report that a novel CAPN3-binding protein, PLEIAD [Platform element for inhibition of autolytic degradation; originally called SIMC1/C5orf25 (SUMO-interacting motif containing protein 1/chromosome 5 open reading frame 25)], suppresses the protease activity of CAPN3. Database analyses showed that PLEIAD homologs, like CAPN3 homologs, are evolutionarily conserved in vertebrates. Furthermore, we found that PLEIAD also interacts with CTBP1 (C-terminal binding protein 1), a transcriptional co-regulator, and CTBP1 is proteolyzed in COS7 cells expressing CAPN3. The identified cleavage sites in CTBP1 suggested that it undergoes functional modification upon its proteolysis by CAPN3, as well as by conventional calpains. These results indicate that PLEIAD can shift its major function from CAPN3 suppression to CAPN3-substrate recruitment, depending on the cellular context. Taken together, our data suggest that PLEIAD is a novel regulatory scaffold for CAPN3, as reflected in its name.
登录
查看更多内容
影响因子：
64.8
作者：
Hanna, Rachel A.;Campbell, Robert L.;Davies, Peter L.
通讯作者：
Davies, Peter L.
影响因子：
16
作者：
Lin, X;Sun, BH;Feng, XH
通讯作者：
Feng, XH
影响因子：
10.5
作者：
Kajimura, Shingo;Seale, Patrick;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
3.4
作者：
Fougerousse, F;Gonin, P;Raymackers, JM
通讯作者：
Raymackers, JM
影响因子：
4.8
作者：
Dammer, Eric B.;Sewer, Marion B.
通讯作者：
Sewer, Marion B.