Hand In Hand: NUB1L Joins to the P97UFD1/NPL4 Complex to Regulate Degradation of NEDD8
Source:
Time: 2015-09-20
NEDD8 is an ubiquitin-like protein modulating some cellular processes by reversible protein modification of substrates as known neddylation. NUB1L (NEDD8 Ultimate Buster-1 Long) is proposed to be one of the modulators of this neddylation. However, the underlying mechanism of this regulatory pathway remains elusive. Recently, researchers from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, elucidated that NUB1L down-regulates neddylation by promoting the proteasomal degradation of NEDD8 through the P97
UFD1/NPL4 complex.
NUB1L specifically interacts with NEDD8 on its key residue Asn51. Thus, NUB1L is capable of promoting the proteasomal degradation of NEDD8, and down-regulating the protein levels of NEDD8 and neddylation. Dr. LIU Shuai and his colleagues, led by Prof. HU Hongyu, discovered a VBM motif in NUB1L, and found that NUB1L interacts with P97 via this motif.
P97 is involved in the proteasomal degradation of NEDD8 by cooperation of its co-factors UFD1 and NPL4. The interaction between the P97
UFD1/NPL4 complex and NEDD8 depended on ATP. It suggests that P97 regulates the association of NPL4 with NEDD8 through conformational changes during ATP hydrolysis. They found that NUB1L joins to the P97
UFD1/NPL4 complex by the interaction with P97. The NUB1L-P97
UFD1/NPL4 complex was probably the key element in the NEDD8-proteasome pathway. NUB1L and P97 down regulated the neddylation of Cullin1 by promoting the degradation of NEDD8. These results provided insights into the molecular mechanism by which NUB1L cooperates with the P97UFD1/NPL4 complex in the modulation of neddylation. Thus, controlling neddylation pathway may be a promising cancer therapeutic strategy.
This study entitled “
NEDD8 Ultimate Buster-1 Long (NUB1L) Promotes Transfer of NEDD8 to Proteasome for Degradation through the P97UFD1/NPL4Complex” was published in
The Journal of Biological Chemistry on October 25, 2013. It was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Chinese Academy of Sciences. (SIBCB)
AUTHOR CONTACT:
HU Hongyu
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Phone: 86-21-54921121;
E-mail:
hyhu@sibcb.ac.cn
The image depicts the NEDD8 protein and neddylation levels modulated by NUB1L and P97UFD1/NPL4. P97 works like a robot engine supplying “energy” during hydrolysis of ATP. NEDD8 is recruited by the UFD1/NPL4 cofactors (one hand), then passed onto NUB1L (the other hand) and finally delivered to the proteasome (the trash bin) for degradation. (Image by Dr. HU Hongyu’s group).
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