Apoptosis Database

Description [+]

Synonyms: CYLD, CYLD, CYLINDROMATOSIS (TURBAN TUMOR SYNDROME)
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
Short gene description: cylindromatosis (turban tumor syndrome) Gene [Source:MGI Symbol;Acc:MGI:1921506]
Family: other
Process: necroptosis,
Pathways: TNF/NF-kappaB signaling,
Criteria: manually curated
Curator comment:
Human ortholog(s): CYLD
WIKI: CYLD-M_musculus

References [+]

Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway.
Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ, Yuan J
Stimulation of death receptors by agonists such as FasL and TNFalpha activates apoptotic cell death in apoptotic-competent conditions or a type of necrotic cell death dependent on RIP1 kinase, termed necroptosis, in apoptotic-deficient conditions. In a genome-wide siRNA screen for regulators of necroptosis, we identify a set of 432 genes that regulate necroptosis, a subset of 32 genes that act downstream and/or as regulators of RIP1 kinase, 32 genes required for death-receptor-mediated apoptosis, and 7 genes involved in both necroptosis and apoptosis. We show that the expression of subsets of the 432 genes is enriched in the immune and nervous systems, and cellular sensitivity to necroptosis is regulated by an extensive signaling network mediating innate immunity. Interestingly, Bmf, a BH3-only Bcl-2 family member, is required for death-receptor-induced necroptosis. Our study defines a cellular signaling network that regulates necroptosis and the molecular bifurcation that controls apoptosis and necroptosis. Cell. 2008 Dec 26;135(7):1311-23.

TNF-alpha induces two distinct caspase-8 activation pathways.
Wang L, Du F, Wang X
The inflammatory response of mammalian cells to TNF-alpha can be switched to apoptosis either by cotreatment with a protein synthesis inhibitor, cycloheximide, or Smac mimetic, a small molecule mimic of Smac/Diablo protein. Cycloheximide promotes caspase-8 activation by eliminating endogenous caspase-8 inhibitor, c-FLIP, while Smac mimetic does so by triggering autodegradation of cIAP1 and cIAP2 (cIAP1/2), leading to the release of receptor interacting protein kinase (RIPK1) from the activated TNF receptor complex to form a caspase-8-activating complex consisting of RIPK1, FADD, and caspase-8. This process also requires the action of CYLD, a RIPK1 K63 deubiquitinating enzyme. RIPK1 is critical for caspase-8 activation-induced by Smac mimetic but dispensable for that triggered by cycloheximide. Moreover, Smac mimetic-induced caspase-8 activation is not blocked by endogenous c-FLIP. These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP. Cell. 2008 May 16;133(4):693-703.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	CAP_GLY	127	203
PFAM A	CAP_GLY	232	303
PFAM A	CAP_GLY	471	539
PFAM A	UCH	588	946

Protein sequence [+]

Structure links:

Evolution [+]

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006412	translation	biological_proccess	IEA
GO:0006511	ubiquitin-dependent protein catabolic process	biological_proccess	IEA
GO:0019941	modification-dependent protein catabolic process	biological_proccess	IEA
GO:0003735	structural constituent of ribosome	mollecular_function	IEA
GO:0004221	ubiquitin thiolesterase activity	mollecular_function	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0008233	peptidase activity	mollecular_function	IEA
GO:0008234	cysteine-type peptidase activity	mollecular_function	IEA
GO:0016787	hydrolase activity	mollecular_function	IEA
GO:0005622	intracellular	cell_component	IEA
GO:0005840	ribosome	cell_component	IEA
GO:0005737	cytoplasm	cell_component	IEA
GO:0048471	perinuclear region of cytoplasm	cell_component	IEA

Check GO Evidence Codes here

Information from other databases [+]

CYLD (Mus musculus)