A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates

被引:917
作者
Kirkin, Vladimir [1 ,2 ,3 ]
Lamark, Trond
Sou, Yu-Shin [4 ]
Bjorkoy, Geir [3 ]
Nunn, Jennifer L. [3 ]
Bruun, Jack-Ansgar [3 ]
Shvets, Elena [5 ]
McEwan, David G. [1 ,2 ]
Clausen, Terje H. [3 ]
Wild, Philipp [1 ,2 ]
Bilusic, Ivana [1 ,2 ]
Theurillat, Jean-Philippe [6 ]
Overvatn, Aud [3 ]
Ishii, Tetsuro [7 ]
Elazar, Zvulun [5 ]
Komatsu, Masaaki [4 ]
Dikic, Ivan [1 ,2 ,8 ]
Johansen, Terje [3 ]
机构
[1] Univ Frankfurt, Inst Biochem 2, D-60590 Frankfurt, Germany
[2] Univ Frankfurt, Cluster Excellence Macromol Complexes, D-60590 Frankfurt, Main, Germany
[3] Univ Tromso, Dept Biochem, Inst Med Biol, N-9037 Tromso, Norway
[4] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Bunkyo Ku, Tokyo 1138613, Japan
[5] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
[6] Univ Zurich Hosp, Inst Surg Pathol, Dept Pathol, CH-8091 Zurich, Switzerland
[7] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan
[8] Mediterranean Inst Life Sci, Tumor Biol Program, Split 21000, Croatia
基金
以色列科学基金会;
关键词
SELECTIVE AUTOPHAGY; STRUCTURAL BASIS; PROTEIN; MICE; NEURODEGENERATION; P62/SQSTM1; CELLS; P62; ACCUMULATION; DISSECTION;
D O I
10.1016/j.molcel.2009.01.020
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
Autophagy is a catabolic process where cytosolic cellular components are delivered to the lysosome for degradation. Recent studies have indicated the existence of specific receptors, such as p62, which link ubiquitinated targets to autophagosomal degradation pathways. Here we show that NBR1 (neighbor of BRCA1 gene 1) is an autophagy receptor containing LC3- and ubiquitin (Ub)-binding domains. NIBR1 is recruited to Ub-positive protein aggregates and degraded by autophagy depending on an LC3-interacting region (LIR) and LC3 family modifiers. Although NBR1 and p62 interact and form oligomers, they can function independently, as shown by autophagosomal clearance of NBR1 in p62-deficient cells. NBR1 was localized to Ub-positive inclusions in patients with liver dysfunction, and depletion of NBR1 abolished the formation of Ub-positive p62 bodies upon puromycin treatment of cells. We propose that NBR1 and p62 act as receptors for selective autophagosomal degradation of ubiquitinated targets.
引用
收藏
页码:505 / 516
页数:12
相关论文
共 28 条
[1]   Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration [J].
Babu, J. Ramesh ;
Seibenhener, M. Lamar ;
Peng, Junmin ;
Strom, Anna-Lena ;
Kemppainen, Robert ;
Cox, Nancy ;
Zhu, Haining ;
Wooten, Michael C. ;
Diaz-Meco, Maria T. ;
Moscat, Jorge ;
Wooten, Marie W. .
JOURNAL OF NEUROCHEMISTRY, 2008, 106 (01) :107-120
[2]   p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death [J].
Bjorkoy, G ;
Lamark, T ;
Brech, A ;
Outzen, H ;
Perander, M ;
Overvatn, A ;
Stenmark, H ;
Johansen, T .
JOURNAL OF CELL BIOLOGY, 2005, 171 (04) :603-614
[3]   Protein folding and misfolding [J].
Dobson, CM .
NATURE, 2003, 426 (6968) :884-890
[4]   Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice [J].
Hara, Taichi ;
Nakamura, Kenji ;
Matsui, Makoto ;
Yamamoto, Akitsugu ;
Nakahara, Yohko ;
Suzuki-Migishima, Rika ;
Yokoyama, Minesuke ;
Mishima, Kenji ;
Saito, Ichiro ;
Okano, Hideyuki ;
Mizushima, Noboru .
NATURE, 2006, 441 (7095) :885-889
[5]   Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B [J].
He, H ;
Dang, YJ ;
Dai, FY ;
Guo, ZK ;
Wu, JX ;
She, XY ;
Pei, Y ;
Chen, YJ ;
Ling, WH ;
Wu, CQ ;
Zhao, SY ;
Liu, JO ;
Yu, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (31) :29278-29287
[6]   Structural basis for sorting mechanism of p62 in selective autophagy [J].
Ichimura, Yoshinobu ;
Kumanomidou, Taichi ;
Sou, Yu-shin ;
Mizushima, Tsunehiro ;
Ezaki, Junji ;
Ueno, Takashi ;
Kominami, Eiki ;
Yamane, Takashi ;
Tanaka, Keiji ;
Komatsu, Masaaki .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (33) :22847-22857
[7]  
KEDA F, 2008, EMBO REP, V9, P536
[8]   Role of ubiquitin- and Ubl-binding proteins in cell signaling [J].
Kirkin, Vladimir ;
Dikic, Ivan .
CURRENT OPINION IN CELL BIOLOGY, 2007, 19 (02) :199-205
[9]   Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice [J].
Komatsu, M ;
Waguri, S ;
Ueno, T ;
Iwata, J ;
Murata, S ;
Tanida, I ;
Ezaki, J ;
Mizushima, N ;
Ohsumi, Y ;
Uchiyama, Y ;
Kominami, E ;
Tanaka, K ;
Chiba, T .
JOURNAL OF CELL BIOLOGY, 2005, 169 (03) :425-434
[10]   Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice [J].
Komatsu, Masaaki ;
Waguri, Satoshi ;
Koike, Masato ;
Sou, Yu-shin ;
Ueno, Takashi ;
Hara, Taichi ;
Mizushima, Noboru ;
Iwata, Jun-ichi ;
Ezaki, Junji ;
Murata, Shigeo ;
Hamazaki, Jun ;
Nishito, Yasumasa ;
Iemura, Shun-ichiro ;
Natsume, Tohru ;
Yanagawa, Toru ;
Uwayama, Junya ;
Warabi, Eiji ;
Yoshida, Hiroshi ;
Ishii, Tetsuro ;
Kobayashi, Akira ;
Yamamoto, Masayuki ;
Yue, Zhenyu ;
Uchiyama, Yasuo ;
Kominami, Eiki ;
Tanaka, Keiji .
CELL, 2007, 131 (06) :1149-1163