DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1

被引:148
作者
Wu, K
Yamoah, K
Dolios, G
Gan-Erdene, T
Tan, PL
Chen, A
Lee, CG
Wei, N
Wilkinson, KD
Wang, R
Pan, ZQ [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA
[3] Emory Univ, Dept Biochem, Atlanta, GA 30322 USA
[4] Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, New Jersey Med Sch, Newark, NJ 07103 USA
[5] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
关键词
D O I
10.1074/jbc.M302888200
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
Nedd8 activates ubiquitination by increasing the efficiency of polyubiquitin chain assembly through its covalent conjugation to cullin molecules. Here we report the isolation, cloning, and characterization of a novel human Nedd8-specific protease called DEN1. Human DEN1 is encoded by AAH31411.1, a previously uncharacterized protein of 212 amino acids that shares homology with the Ulp1 cysteinyl SUMO deconjugating enzyme family. Recombinant human DEN1, purified from bacteria, selectively binds to Nedd8 and hydrolyzes C-terminal derivatives of Nedd8. Interestingly, DEN1 deconjugates cullin 1 (CUL1)-Nedd8 in a concentration-dependent manner. At a low concentration, DEN1 processes hyper-neddylated CUL1 to yield a mononeddylated form, which presumably contains the Lys720(CUL1)- Nedd8 linkage. At elevated concentrations, DEN1 is able to complete the removal of Nedd8 from CUL1. These activities distinguish DEN1 from the COP9 signalosome, which is capable of efficiently cleaving the Lys-720(CUL1)-Nedd8 conjugate, but lacks Nedd8 C-terminal hydrolytic activity and poorly processes hyperneddylated CUL1. These results suggest a unique role for DEN1 in regulating the modification of cullins by Nedd8.
引用
收藏
页码:28882 / 28891
页数:10
相关论文
共 41 条
[11]   Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde [J].
Hu, M ;
Li, PW ;
Li, MY ;
Li, WY ;
Yao, TT ;
Wu, JW ;
Gu, W ;
Cohen, RE ;
Shi, YG .
CELL, 2002, 111 (07) :1041-1054
[12]   Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 angstrom resolution [J].
Johnston, SC ;
Larsen, CN ;
Cook, WJ ;
Wilkinson, KD ;
Hill, CP .
EMBO JOURNAL, 1997, 16 (13) :3787-3796
[13]   The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2 [J].
Kamura, T ;
Conrad, MN ;
Yan, Q ;
Conaway, RC ;
Conaway, JW .
GENES & DEVELOPMENT, 1999, 13 (22) :2928-2933
[14]   NEDD8 recruits E2-ubiquitin to SCF E3 ligase [J].
Kawakami, T ;
Chiba, T ;
Suzuki, T ;
Iwai, K ;
Yamanaka, K ;
Minato, N ;
Suzuki, H ;
Shimbara, N ;
Hidaka, Y ;
Osaka, F ;
Omata, M ;
Tanaka, K .
EMBO JOURNAL, 2001, 20 (15) :4003-4012
[15]   A new protease required for cell-cycle progression in yeast [J].
Li, SJ ;
Hochstrasser, M .
NATURE, 1999, 398 (6724) :246-251
[16]   NEDD8 modification of CUL1 short article dissociates p120CAND1, an inhibitor of CULl-SKP1 binding and SCIF ligases [J].
Liu, JD ;
Furukawa, M ;
Matsumoto, T ;
Xiong, Y .
MOLECULAR CELL, 2002, 10 (06) :1511-1518
[17]   Promotion of NEDD8-CUL1 conjugate cleavage by COP9 signalosome [J].
Lyapina, S ;
Cope, G ;
Shevchenko, A ;
Serino, G ;
Tsuge, T ;
Zhou, CS ;
Wolf, DA ;
Wei, N ;
Shevchenko, A ;
Deshaies, RJ .
SCIENCE, 2001, 292 (5520) :1382-1385
[18]   Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast [J].
Mossessova, E ;
Lima, CD .
MOLECULAR CELL, 2000, 5 (05) :865-876
[19]   An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells [J].
Ohh, M ;
Kim, WY ;
Moslehi, JJ ;
Chen, YZ ;
Chau, V ;
Read, MA ;
Kaelin, WG .
EMBO REPORTS, 2002, 3 (02) :177-182
[20]   ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity [J].
Ohta, T ;
Michel, JJ ;
Schottelius, AJ ;
Xiong, Y .
MOLECULAR CELL, 1999, 3 (04) :535-541