PMID- 17053834
OWN - NLM
STAT- MEDLINE
DCOM- 20061218
LR  - 20220316
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 116
IP  - 11
DP  - 2006 Nov
TI  - Impaired regulation of NF-kappaB and increased susceptibility to 
      colitis-associated tumorigenesis in CYLD-deficient mice.
PG  - 3042-9
AB  - Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients 
      with familial cylindromatosis, a condition characterized by numerous benign 
      adnexal tumors. However, the regulatory function of CYLD remains unsettled. Here 
      we show that the development of B cells, T cells, and myeloid cells was 
      unaffected in CYLD-deficient mice, but that the activation of these cells with 
      mediators of innate and adaptive immunity resulted in enhanced NF-kappaB and JNK 
      activity associated with increased TNF receptor-associated factor 2 (TRAF2) and 
      NF-kappaB essential modulator (NEMO) ubiquitination. CYLD-deficient mice were 
      more susceptible to induced colonic inflammation and showed a dramatic increase 
      in the incidence of tumors compared with controls in a colitis-associated cancer 
      model. These results suggest that CYLD limits inflammation and tumorigenesis by 
      regulating ubiquitination in vivo.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Laboratory of Host Defenses, National Institute of Allergy and Infectious 
      Diseases, NIH, Bethesda, Maryland 20892, USA.
FAU - Stirling, Brigid
AU  - Stirling B
FAU - Temmerman, Stephane T
AU  - Temmerman ST
FAU - Ma, Chi A
AU  - Ma CA
FAU - Fuss, Ivan J
AU  - Fuss IJ
FAU - Derry, Jonathan M J
AU  - Derry JM
FAU - Jain, Ashish
AU  - Jain A
LA  - eng
PT  - Journal Article
DEP - 20061019
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NEMO protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Ubiquitin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.4.19.12 (CYLD protein, mouse)
RN  - EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Animals
MH  - Cell Transformation, Neoplastic/genetics/*metabolism/*pathology
MH  - Colitis/complications/genetics/*metabolism/*pathology
MH  - Colonic Neoplasms/etiology/genetics/metabolism/pathology
MH  - Cysteine Endopeptidases/deficiency/genetics/*metabolism
MH  - Cytokines/biosynthesis
MH  - Deubiquitinating Enzyme CYLD
MH  - Enzyme Activation
MH  - Genetic Predisposition to Disease/*genetics
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/*metabolism
MH  - Phenotype
MH  - Protein Binding
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Ubiquitin/metabolism
PMC - PMC1616194
EDAT- 2006/10/21 09:00
MHDA- 2006/12/19 09:00
PMCR- 2006/11/01
CRDT- 2006/10/21 09:00
PHST- 2006/04/05 00:00 [received]
PHST- 2006/09/12 00:00 [accepted]
PHST- 2006/10/21 09:00 [pubmed]
PHST- 2006/12/19 09:00 [medline]
PHST- 2006/10/21 09:00 [entrez]
PHST- 2006/11/01 00:00 [pmc-release]
AID - 28746 [pii]
AID - 10.1172/JCI28746 [doi]
PST - ppublish
SO  - J Clin Invest. 2006 Nov;116(11):3042-9. doi: 10.1172/JCI28746. Epub 2006 Oct 19.