Dev Cell. 2007 Sep;13(3):446-54.

Tumor suppressor CYLD regulates JNK-induced cell death in Drosophila.

Xue L, Igaki T, Kuranaga E, Kanda H, Miura M, Xu T.

Source

Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06536, USA.

Abstract

CYLD encodes a tumor suppressor that is mutated in familial cylindromatosis. Despite biochemical and cell culture studies, the physiological functions of CYLD in animal development and tumorigenesis remain poorly understood. To address these questions, we generated Drosophila CYLD (dCYLD) mutant and transgenic flies expressing wild-type and mutant dCYLD proteins. Here we show that dCYLD is essential for JNK-dependent oxidative stress resistance and normal lifespan. Furthermore, dCYLD regulates TNF-induced JNK activation and cell death through dTRAF2, which acts downstream of the TNF receptor Wengen and upstream of the JNKK kinase dTAK1. We show that dCYLD encodes a deubiquitinating enzyme that deubiquitinates dTRAF2 and prevents dTRAF2 from ubiquitin-mediated proteolytic degradation. These data provide a molecular mechanism for the tumor suppressor function of this evolutionary conserved molecule by indicating that dCYLD plays a critical role in modulating TNF-JNK-mediated cell death.

Comment in

Dev Cell. 2007 Nov;13(5):601-3.

PMID:: 17765686; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances

Publication Types

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Supplemental Content

Save items

Related citations in PubMed

Negative regulation of JNK signaling by the tumor suppressor CYLD. [J Biol Chem. 2004]
Negative regulation of JNK signaling by the tumor suppressor CYLD.
Reiley W, Zhang M, Sun SC. J Biol Chem. 2004 Dec 31; 279(53):55161-7. Epub 2004 Oct 20.
JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila. [Cell Death Differ. 2006]
JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila.
Lee JH, Koh H, Kim M, Park J, Lee SY, Lee S, Chung J. Cell Death Differ. 2006 Jul; 13(7):1110-22. Epub 2005 Nov 4.
Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. [Nat Cell Biol. 2002]
Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila.
Kuranaga E, Kanuka H, Igaki T, Sawamoto K, Ichijo H, Okano H, Miura M. Nat Cell Biol. 2002 Sep; 4(9):705-10.
Review CYLD: a multifunctional deubiquitinase. [Fly (Austin). 2007]
Review CYLD: a multifunctional deubiquitinase.
Glittenberg M, Ligoxygakis P. Fly (Austin). 2007 Nov-Dec; 1(6):330-2. Epub 2007 Nov 10.
Review Tumor suppressor CYLD: negative regulation of NF-kappaB signaling and more. [Cell Mol Life Sci. 2008]
Review Tumor suppressor CYLD: negative regulation of NF-kappaB signaling and more.
Courtois G. Cell Mol Life Sci. 2008 Apr; 65(7-8):1123-32.

See reviews... See all...

Cited by 10 PubMed Central articles

The HIV-1 Vpu Protein Induces Apoptosis in Drosophila via Activation of JNK Signaling. [PLoS One. 2012]
The HIV-1 Vpu Protein Induces Apoptosis in Drosophila via Activation of JNK Signaling.
Marchal C, Vinatier G, Sanial M, Plessis A, Pret AM, Limbourg-Bouchon B, Théodore L, Netter S. PLoS One. 2012; 7(3):e34310. Epub 2012 Mar 29.
Conserved metabolic energy production pathways govern Eiger/TNF-induced nonapoptotic cell death. [Proc Natl Acad Sci U S A. 2011]
Conserved metabolic energy production pathways govern Eiger/TNF-induced nonapoptotic cell death.
Kanda H, Igaki T, Okano H, Miura M. Proc Natl Acad Sci U S A. 2011 Nov 22; 108(47):18977-82. Epub 2011 Nov 7.
Serum response factor controls CYLD expression via MAPK signaling pathway. [PLoS One. 2011]
Serum response factor controls CYLD expression via MAPK signaling pathway.
Liang G, Ahlqvist K, Pannem R, Posern G, Massoumi R. PLoS One. 2011 May 5; 6(5):e19613. Epub 2011 May 5.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Tumor suppressor CYLD regulates JNK-induced cell death in Drosophila.
Tumor suppressor CYLD regulates JNK-induced cell death in Drosophila.
Dev Cell. 2007 Sep ;13(3):446-54.

PubMed
Electromagnetic fields (EMF): do they play a role in children's environmental he...
Electromagnetic fields (EMF): do they play a role in children's environmental health (CEH)?
Int J Hyg Environ Health. 2007 Oct ;210(5):635-44. Epub 2007 Aug 31 .

PubMed
Mobilization of human CD34+ CD133+ and CD34+ CD133(-) stem cells in vivo by cons...
Mobilization of human CD34+ CD133+ and CD34+ CD133(-) stem cells in vivo by consumption of an extract from Aphanizomenon flos-aquae--related to modulation of CXCR4 expression by an L-selectin ligand?
Cardiovasc Revasc Med. 2007 Jul-Sep ;8(3):189-202.

PubMed
Are there distinctive sleep problems in Angelman syndrome?
Are there distinctive sleep problems in Angelman syndrome?
Sleep Med. 2008 May ;9(4):434-41. Epub 2007 Aug 31 .

PubMed
Piecing together the puzzle of basal forebrain anatomy.
Piecing together the puzzle of basal forebrain anatomy.
Adv Exp Med Biol. 1991 ;295:1-42.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: