PMID- 24163370
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 50
DP  - 2013 Dec 13
TI  - The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting 
      complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the metaphase 
      to anaphase transition.
PG  - 35637-50
LID - 10.1074/jbc.M113.472076 [doi]
AB  - NEDD4-like ubiquitin ligase 2 (NEDL2) is a HECT type ubiquitin ligase. NEDL2 
      enhances p73 transcriptional activity and degrades ATR kinase in lamin 
      misexpressed cells. Compared with the important functions of other HECT type 
      ubiquitin ligase, there is less study concerning the function and regulation of 
      NEDL2. Using primary antibody immunoprecipitation and mass spectrometry, we 
      identify a list of potential proteins that are putative NEDL2-interacting 
      proteins. The candidate list contains many of mitotic proteins, especially 
      including several subunits of anaphase-promoting complex/cyclosome (APC/C) and 
      Cdh1, an activator of APC/C. Cdh1 can interact with NEDL2 in vivo and in vitro. 
      Cdh1 recognizes one of the NEDL2 destruction boxes (R(740)GSL(743)) and targets 
      it for degradation in an APC/C-dependent manner during mitotic exit. 
      Overexpression of Cdh1 reduces the protein level of NEDL2, whereas knockdown of 
      Cdh1 increases the protein level of NEDL2 but has no effect on the NEDL2 mRNA 
      level. NEDL2 associates with mitotic spindles, and its protein level reaches a 
      maximum in mitosis. The function of NEDL2 during mitosis is essential because 
      NEDL2 depletion prolongs metaphase, and overexpression of NEDL2 induces 
      chromosomal lagging. Elevated expression of NEDL2 protein and mRNA are both found 
      in colon cancer and cervix cancer. We conclude that NEDL2 is a novel substrate of 
      APC/C-Cdh1 as cells exit mitosis and functions as a regulator of the metaphase to 
      anaphase transition. Its overexpression may contribute to tumorigenesis.
FAU - Lu, Li
AU  - Lu L
AD  - From the State Key Laboratory of Proteomics, Beijing Proteome Research Center, 
      Beijing Institute of Radiation Medicine, Beijing 100850, China.
FAU - Hu, Shaohua
AU  - Hu S
FAU - Wei, Rongfei
AU  - Wei R
FAU - Qiu, Xiao
AU  - Qiu X
FAU - Lu, Kefeng
AU  - Lu K
FAU - Fu, Yesheng
AU  - Fu Y
FAU - Li, Hongchang
AU  - Li H
FAU - Xing, Guichun
AU  - Xing G
FAU - Li, Dong
AU  - Li D
FAU - Peng, Ruiyun
AU  - Peng R
FAU - He, Fuchu
AU  - He F
FAU - Zhang, Lingqiang
AU  - Zhang L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131025
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (CDH1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.3.2.26 (HECW2 protein, human)
RN  - EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Amino Acid Motifs
MH  - *Anaphase
MH  - Anaphase-Promoting Complex-Cyclosome/*metabolism
MH  - Antigens, CD
MH  - Cadherins/*metabolism
MH  - Carcinogenesis
MH  - Cell Line
MH  - Chromosome Aberrations
MH  - Enzyme Activation
MH  - Humans
MH  - *Metaphase
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - *Proteolysis
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - Spindle Apparatus/metabolism
MH  - Time Factors
MH  - Ubiquitin-Protein Ligases/chemistry/deficiency/genetics/*metabolism
PMC - PMC3861616
OTO - NOTNLM
OT  - APC/C
OT  - Cell Cycle
OT  - Mitosis
OT  - Protein Degradation
OT  - Tumor
OT  - Ubiquitin Ligase
EDAT- 2013/10/29 06:00
MHDA- 2014/02/14 06:00
PMCR- 2014/12/13
CRDT- 2013/10/29 06:00
PHST- 2013/10/29 06:00 [entrez]
PHST- 2013/10/29 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
PHST- 2014/12/13 00:00 [pmc-release]
AID - S0021-9258(19)54288-0 [pii]
AID - M113.472076 [pii]
AID - 10.1074/jbc.M113.472076 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Dec 13;288(50):35637-50. doi: 10.1074/jbc.M113.472076. Epub 
      2013 Oct 25.