VCIP135 deubiquitinase and its binding protein, WAC, in p97ATPase-mediated membrane fusion

被引：34

作者：

Totsukawa, Go ^{[1
,2
]}

Kaneko, Yayoi ^{[1
,2
]}

Uchiyama, Keiji ^{[2
,3
]}

Toh, Hiroyuki ^{[4
]}

Tamura, Kaori ^{[1
]}

Kondo, Hisao ^{[1
,2
]}

机构：

[1] Kyushu Univ, Dept Mol Cell Biol, Fac Med Sci, Fukuoka 8128582, Japan

[2] Mitsubishi Kagaku Inst Life Sci, Tokyo, Japan

[3] Univ Tokushima, Inst Enzyme Res, Tokushima 770, Japan

[4] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Tokyo, Japan

来源：

EMBO JOURNAL | 2011年 / 30卷 / 17期

关键词：

ER; Golgi; p37; p47; NF-KAPPA-B; MITOTIC GOLGI FRAGMENTS; EDITING ENZYME A20; ENDOPLASMIC-RETICULUM; CELL-CYCLE; IN-VITRO; P47; P97; COMPLEXES; CISTERNAE;

D O I：

10.1038/emboj.2011.260

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Two distinct p97 membrane fusion pathways are required for Golgi biogenesis: the p97/p47 and p97/p37 pathways. VCIP135 is necessary for both pathways, while its deubiquitinating activity is required only for the p97/p47 pathway. We have now identified a novel VCIP135-binding protein, WAC. WAC localizes to the Golgi as well as the nucleus. In Golgi membranes, WAC is involved in a complex containing VCIP135 and p97. WAC directly binds to VCIP135 and increases its deubiquitinating activity. siRNA experiments revealed that WAC is required for Golgi biogenesis. In an in vitro Golgi reformation assay, WAC was necessary only for p97/p47-mediated Golgi reassembly, but not for p97/p37-mediated reassembly. WAC is hence thought to function in p97/p47-mediated Golgi membrane fusion by activating the deubiquitinating function of VCIP135. We also showed that the two p97 pathways function in ER membrane fusion as well. An in vitro ER reformation assay revealed that both pathways required VCIP135 but not its deubiquitinating activity for their ER membrane fusion. This was consistent with the finding that WAC is unnecessary for p97-mediated ER membrane fusion. The EMBO Journal (2011) 30, 3581-3593. doi:10.1038/emboj.2011.260; Published online 2 August 2011

引用

页码：3581 / 3593

页数：13

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