Ancient Ubiquitous Protein 1 (AUP1) Localizes to Lipid Droplets and Binds the E2 Ubiquitin Conjugase G2 (Ube2g2) via Its G2 Binding Region

被引:90
作者
Spandl, Johanna [1 ]
Lohmann, Daniel [1 ]
Kuerschner, Lars [1 ]
Moessinger, Christine [1 ]
Thiele, Christoph [1 ]
机构
[1] Univ Bonn, Life & Med Sci Inst, D-53115 Bonn, Germany
关键词
ENDOPLASMIC-RETICULUM; CUE DOMAIN; MEMBRANE; DEGRADATION; IDENTIFICATION; PATHWAY; CELLS; DISLOCATION; REDUCTASE; BODIES;
D O I
10.1074/jbc.M110.190785
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
Lipid droplets (LDs), the major intracellular storage sites for neutral lipids, consist of a neutral lipid core surrounded by a phospholipid monolayer membrane. In addition to their function in lipid storage, LDs participate in lipid biosynthesis and recently were implicated in proteasomal protein degradation and autophagy. To identify components of the protein degradation machinery on LDs, we studied several candidates identified in previous LD proteome analyses. Here, we demonstrate that the highly conserved and broadly expressed ancient ubiquitous protein 1 (AUP1) localizes to LDs, where it integrates into the LD surface in a monotopic fashion with both termini facing the cytosol. AUP1 contains a C-terminal domain with strong homology to a domain known as G2BR, which binds E2 ubiquitin conjugases. We show that AUP1, by means of its G2BR domain, binds to Ube2g2. This binding is abolished by deletion or mutation of the G2BR domain, although the LD localization of AUP1 is not affected. The presence of the AUP1-Ube2g2 complex at LDs provides a direct molecular link between LDs and the cellular ubiquitination machinery.
引用
收藏
页码:5599 / 5606
页数:8
相关论文
共 59 条
[1]   Identification and characterization of major lipid particle proteins of the yeast Saccharomyces cerevisiae [J].
Athenstaedt, K ;
Zweytick, D ;
Jandrositz, A ;
Kohlwein, SD ;
Daum, G .
JOURNAL OF BACTERIOLOGY, 1999, 181 (20) :6441-6448
[2]   Dynamic activity of lipid droplets: Protein phosphorylation and GTP-Mediated protein translocation [J].
Bartzt, Rene ;
Zehmer, John K. ;
Zhu, Meifang ;
Chen, Yue ;
Serrero, Ginette ;
Zhao, Yingming ;
Liu, Pingsheng .
JOURNAL OF PROTEOME RESEARCH, 2007, 6 (08) :3256-3265
[3]   Cue1p is an activator of Ubc7p E2 activity in vitro and in vivo [J].
Bazirgan, Omar A. ;
Hampton, Randolph Y. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (19) :12797-12810
[4]   An intimate collaboration between peroxisomes and lipid bodies [J].
Binns, Derk ;
Januszewski, Tom ;
Chen, Yue ;
Hill, Justin ;
Markin, Vladislav S. ;
Zhao, Yingming ;
Gilpin, Christopher ;
Chapman, Kent D. ;
Anderson, Richard G. W. ;
Goodman, Joel M. .
JOURNAL OF CELL BIOLOGY, 2006, 173 (05) :719-731
[5]  
BLANCHETTEMACKIE EJ, 1995, J LIPID RES, V36, P1211
[6]   Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes [J].
Brasaemle, DL ;
Dolios, G ;
Shapiro, L ;
Wang, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (45) :46835-46842
[7]   The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain,, RING finger, and an E2-binding site [J].
Chen, B ;
Mariano, J ;
Tsai, YC ;
Chan, AH ;
Cohen, M ;
Weissman, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (02) :341-346
[8]   The Transmembrane Segment of a Tail-anchored Protein Determines Its Degradative Fate through Dislocation from the Endoplasmic Reticulum [J].
Claessen, Jasper H. L. ;
Mueller, Britta ;
Spooner, Eric ;
Pivorunas, Valerie L. ;
Ploegh, Hidde L. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (27) :20732-20739
[9]   Allosteric Activation of E2-RING Finger-Mediated Ubiquitylation by a Structurally Defined Specific E2-Binding Region of gp78 [J].
Das, Ranabir ;
Mariano, Jennifer ;
Tsai, Yien Che ;
Kalathur, Ravi C. ;
Kostova, Zlatka ;
Li, Jess ;
Tarasov, Sergey G. ;
McFeeters, Robert L. ;
Altieri, Amanda S. ;
Ji, Xinhua ;
Byrd, R. Andrew ;
Weissman, Allan M. .
MOLECULAR CELL, 2009, 34 (06) :674-685
[10]   Fixation methods for the study of lipid droplets by immunofluorescence microscopy [J].
DiDonato, D ;
Brasaemle, DL .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2003, 51 (06) :773-780