Site-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosis.
Site-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosis.
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DOI：
10.1083/jcb.200706034
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发表时间：
2007-12-03
影响因子：
7.8
通讯作者：
Fuchs, Serge Y.
中科院分区：
文献类型：
--
作者：
Kumar, K. G. Suresh;Barriere, Herve;Carbone, Christopher J.;Liu, Jianghuai;Swaminathan, Gayathri;Xu, Ping;Li, Ying;Baker, Darren P.;Peng, Junmin;Lukacs, Gergely L.;Fuchs, Serge Y.
配体诱导的内吞作用和同源受体的溶酶体降解调节细胞信号传导的程度。沿着招募适配蛋白复合物2（AP 2）-网格蛋白分子的线性内吞基序，受体的单泛素化已成为主要的内吞信号。通过研究I型干扰素（IFN）-α/β受体1（IFNAR 1）亚基的泛素依赖性溶酶体降解，我们发现IFNAR 1通过Lys 48和Lys 63连接的链被聚泛素化。SCFβTrcp（Skp 1-Cullin 1-F-box复合物）E3泛素连接酶介导细胞中IFNAR 1的泛素化和降解，可在体外结合两种类型的链。虽然任一聚泛素连接足以进行内化后分选，但两种类型的链都是必需的，但不足以进行稳健的IFNAR 1周转和内化。这些过程也依赖于泛素受体赖氨酸与线性内吞基序的接近程度及其完整性。此外，IFNAR 1的泛素化促进其与AP 2适应素复合物的相互作用，这是IFNAR 1的稳健内化所需的，暗示位点特异性泛素化和线性内吞基序之间的合作调节这一过程。
Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent of cell signaling. Along with linear endocytic motifs that recruit the adaptin protein complex 2 (AP2)–clathrin molecules, monoubiquitination of receptors has emerged as a major endocytic signal. By investigating ubiquitin-dependent lysosomal degradation of the interferon (IFN)-α/β receptor 1 (IFNAR1) subunit of the type I IFN receptor, we reveal that IFNAR1 is polyubiquitinated via both Lys48- and Lys63-linked chains. The SCFβTrcp (Skp1–Cullin1–F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro. Although either polyubiquitin linkage suffices for postinternalization sorting, both types of chains are necessary but not sufficient for robust IFNAR1 turnover and internalization. These processes also depend on the proximity of ubiquitin-acceptor lysines to a linear endocytic motif and on its integrity. Furthermore, ubiquitination of IFNAR1 promotes its interaction with the AP2 adaptin complex that is required for the robust internalization of IFNAR1, implicating cooperation between site-specific ubiquitination and the linear endocytic motif in regulating this process.
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影响因子：
16
作者：
Ea, CK;Deng, L;Chen, ZJJ
通讯作者：
Chen, ZJJ
影响因子：
10.5
作者：
Jin, JP;Shirogane, T;Harper, JW
通讯作者：
Harper, JW
影响因子：
21.3
作者：
Hoeller, D;Crosetto, N;Dikic, I
通讯作者：
Dikic, I
影响因子：
21.3
作者：
Haglund, K;Sigismund, S;Dikic, I
通讯作者：
Dikic, I
DOI：
10.1073/pnas.91.20.9602
发表时间：
1994-09-27
影响因子：
11.1
作者：
CONSTANTINESCU, SN;CROZE, E;PFEFFER, LM
通讯作者：
PFEFFER, LM