PMID- 17968316
OWN - NLM
STAT- MEDLINE
DCOM- 20080501
LR  - 20191210
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 17
DP  - 2008 Apr 10
TI  - COP1D, an alternatively spliced constitutive photomorphogenic-1 (COP1) product, 
      stabilizes UV stress-induced c-Jun through inhibition of full-length COP1.
PG  - 2401-11
AB  - COP1 is an evolutionarily conserved RING-finger ubiquitin ligase acting within a 
      Cullin-RING ligase (CRL) complex that promotes polyubiquitination of c-Jun and 
      p53. Stability of the above substrates is affected by post-translational changes 
      priming the proteins for polyubiquitination and proteasome-dependent degradation. 
      However, degradation of both substrates is controlled indirectly by signaling 
      pathways affecting the E3 ligases involved in their polyubiquitination. Here, we 
      report the identification of COP1D, a ubiquitously expressed splice variant of 
      COP1 lacking a portion of a coiled-coil region involved in intermolecular 
      associations. While being unable to associate with other components of the CRL 
      complex, COP1D exerts a dominant-negative function over the full-length protein, 
      due to its ability to heterodimerize with COP1 and sequester it from the 
      enzymatically active complex. Ectopic expression of COP1D antagonizes the 
      function of COP1, while its selective downregulation by RNA interference promotes 
      more efficient degradation of c-Jun and p53 by the full-length protein. The 
      COP1/COP1D mRNA ratio is modulated by UV stress and a decreased COP1/COP1D ratio 
      correlates with elevated c-Jun, but not p53 protein levels in invasive ductal 
      breast cancer. Thus, dynamic changes of the COP1/COP1D ratio provide an 
      additional level of regulation of the half-life of the substrates of this E3 
      ligase under homeostatic or pathological conditions.
FAU - Savio, M G
AU  - Savio MG
AD  - Unit of Leukocyte Biology, Vita-Salute San Raffaele University School of 
      Medicine, DIBIT-Scientific Institute San Raffaele, Milano, Italy.
FAU - Rotondo, G
AU  - Rotondo G
FAU - Maglie, S
AU  - Maglie S
FAU - Rossetti, G
AU  - Rossetti G
FAU - Bender, J R
AU  - Bender JR
FAU - Pardi, R
AU  - Pardi R
LA  - eng
GR  - R01 HL43331/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071029
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (COP1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Base Sequence
MH  - Breast Neoplasms/genetics/metabolism
MH  - Cell Line
MH  - Down-Regulation
MH  - Enzyme Stability/radiation effects
MH  - HeLa Cells
MH  - Health
MH  - Humans
MH  - Isoenzymes/genetics/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - RNA, Messenger/genetics
MH  - Transcription, Genetic/genetics
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
EDAT- 2007/10/31 09:00
MHDA- 2008/05/02 09:00
CRDT- 2007/10/31 09:00
PHST- 2007/10/31 09:00 [pubmed]
PHST- 2008/05/02 09:00 [medline]
PHST- 2007/10/31 09:00 [entrez]
AID - 1210892 [pii]
AID - 10.1038/sj.onc.1210892 [doi]
PST - ppublish
SO  - Oncogene. 2008 Apr 10;27(17):2401-11. doi: 10.1038/sj.onc.1210892. Epub 2007 Oct 
      29.