PMID- 23884858
OWN - NLM
STAT- MEDLINE
DCOM- 20131029
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 122
IP  - 10
DP  - 2013 Sep 5
TI  - COP1 targets C/EBPalpha for degradation and induces acute myeloid leukemia via Trib1.
PG  - 1750-60
LID - 10.1182/blood-2012-12-476101 [doi]
AB  - The ubiquitin ligase constitutively photomorphogenic 1 (COP1) is involved in many 
      biological responses in mammalian cells, but its role in tumorigenesis remains 
      unclear. Here we show that COP1 is a ubiquitin ligase for the tumor suppressor 
      CCAAT/enhancer-binding protein (C/EBPalpha) and promotes its degradation in vivo, 
      thereby blocking myeloid differentiation of hematopoietic cells for 
      tumorigenesis. In this process, mammalian homolog of Tribbles, Trib1, which 
      contains a COP1-binding motif, is essential for down-regulation of C/EBPalpha 
      expression. Murine bone marrow transplantation experiments showed that 
      coexpression of COP1 accelerates development of acute myeloid leukemia induced by 
      Trib1, which pathologically resembles that of p42C/EBPalpha-deficient mice. 
      Interestingly, coexpression of ligase activity-deficient COP1 mutant abrogated 
      Trib1-induced leukemogenesis. These results indicate that COP1 and Trib1 act as 
      an oncoprotein complex functioning upstream of C/EBPalpha, and its ligase activity is 
      crucial for leukemogenesis.
FAU - Yoshida, Akihiro
AU  - Yoshida A
AD  - Department of Tumor Cell Biology, Graduate School of Biological Sciences, Nara 
      Institute of Science and Technology, Ikoma, Nara, Japan.
FAU - Kato, Jun-Ya
AU  - Kato JY
FAU - Nakamae, Ikuko
AU  - Nakamae I
FAU - Yoneda-Kato, Noriko
AU  - Yoneda-Kato N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130724
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Mutant Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trib1 protein, mouse)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - EC 2.3.2.27 (COP1 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Alternative Splicing/drug effects
MH  - Animals
MH  - Bone Marrow Transplantation
MH  - CCAAT-Enhancer-Binding Protein-alpha/*metabolism
MH  - Cell Differentiation/drug effects
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - Granulocytes/drug effects/metabolism/pathology
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Leukemia, Myeloid, Acute/*metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutant Proteins/metabolism
MH  - Mutation/genetics
MH  - NIH 3T3 Cells
MH  - Nuclear Proteins/*metabolism
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - *Proteolysis/drug effects
MH  - Ubiquitin-Protein Ligases/*metabolism
EDAT- 2013/07/26 06:00
MHDA- 2013/10/30 06:00
CRDT- 2013/07/26 06:00
PHST- 2013/07/26 06:00 [entrez]
PHST- 2013/07/26 06:00 [pubmed]
PHST- 2013/10/30 06:00 [medline]
AID - S0006-4971(20)53514-3 [pii]
AID - 10.1182/blood-2012-12-476101 [doi]
PST - ppublish
SO  - Blood. 2013 Sep 5;122(10):1750-60. doi: 10.1182/blood-2012-12-476101. Epub 2013 
      Jul 24.