ATF4 degradation relies on a phosphorylation-dependent interaction with the SCFβTrCP ubiquitin ligase
ATF4 degradation relies on a phosphorylation-dependent interaction with the SCFβTrCP ubiquitin ligase
复制标题
DOI：
10.1128/mcb.21.6.2192-2202.2001
复制
发表时间：
2001-03-01
影响因子：
5.3
通讯作者：
Margottin-Goguet, F
中科院分区：
文献类型：
--
作者：
Lassot, I;Ségéral, E;Margottin-Goguet, F
泛素-蛋白酶体途径通过蛋白质降解调节基因表达。在这里！我们表明，F-box蛋白β TrCP，SCF E3泛素连接酶的受体组分，负责I κ B α和β-连环蛋白降解，与转录因子的ATF-CREB bZIP家族的成员ATF 4共定位于细胞核中，并控制其稳定性。这两种蛋白之间的关联依赖于ATF 4磷酸化和存在于DSGXXXS背景下的ATF 4丝氨酸残基219，其与β TrCP的其他底物中发现的基序相似但不相同。HeLa细胞中ATM泛素化在β TrCP存在下增强。F-box缺失的β TrCP蛋白表现为负转显性突变体，其抑制ATF 4泛素化和降解，随后增强其在环AMP介导的转录中的活性。ATF 4代表SCF β TrCP复合物的新底物，SCF β TrCP复合物是迄今为止鉴定的第一种用于控制bZIP转录因子降解的哺乳动物E3泛素连接酶。
The ubiquitin-proteasome pathway regulates gene expression through protein degradation. Here! we show that the F-box protein beta TrCP, the receptor component of the SCF E3 ubiquitin ligase responsible for I kappaB alpha and beta -catenin degradation, is colocalized in the nucleus with ATF4, a member of the ATF-CREB bZIP family of transcription factors, and controls its stability. Association between the two proteins depends on ATF4 phosphorylation and on ATF4 serine residue 219 present in the context of DSGXXXS, which is similar but not identical to the motif found in other substrates of beta TrCP. ATM ubiquitination in HeLa cells is enhanced in the presence of beta TrCP. The F-box-deleted beta TrCP protein behaves as a negative transdominant mutant that inhibits ATF4 ubiquitination and degradation and, subsequently, enhances its activity in cyclic AMP-mediated transcription ATF4 represents a novel substrate far the SCFbeta TrCP complex, which is the first mammalian E3 ubiquitin ligase identified so far for the control of the degradation of a bZIP transcription factor.