Recombinant Human Nucleolar protein 3 (NOL3)

Function

Functions as an apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly (By similarity). Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation (By similarity). Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors (PubMed:15004034). Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis (PubMed:15509781). Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation (By similarity). Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner (By similarity). Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I (By similarity). Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (By similarity). Inhibits too myoblast differentiation through caspase inhibition (By similarity)

Subcellular Location

Cytoplasm; Mitochondrion; Sarcoplasmic reticulum; Membrane (Lipid-anchor)

Disease Association

Myoclonus, familial, 1 (MYOCL1) : An autosomal dominant neurologic condition characterized by adult onset of cortical myoclonus manifest as involuntary jerks or movements affecting the face and limbs. Affected individuals can also experience falls without seizure activity or loss of consciousness. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Highly expressed in heart and skeletal muscle. Detected at low levels in placenta, liver, kidney and pancreas

Subunit

Oligomerizes (via CARD doamin). Interacts (via CARD domain) with CASP2; inhibits CASP2 activity in a phosphorylation-dependent manner. Interacts with CASP8; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium. Interacts with TFPT; translocates NOL3 into the nucleus and negatively regulated TFPT-induced cell death (By similarity). Interacts directly (via CARD domain) with FAS and FADD (via DED domain); inhibits death-inducing signaling complex death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (By similarity). Interacts (via CARD domain) with BAX (via a C-terminal 33 residues); inhibits BAX activation and translocation and consequently cytochrome c release from mitochondria. Interacts with PPM1G; may dephosphorylate NOL3 (By similarity). Interacts (via CARD domain) with BBC3 (via BH3 domain); preventing the association of BBC3 with BCL2 and resulting in activation of CASP8 (By similarity). Interacts (via CARD domain) with BAD(via BH3 domain); preventing the association of BAD with BCL2 (By similarity). Interacts directly (via CARD domain) with TNFRSF1A; inhibits TNF-signaling pathway (By similarity). Isoform 1 binds to SFRS9/SRp30C

• Koseki T. et al. ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases. — Proc. Natl. Acad. Sci. U.S.A. (1998)
• Stoss O. et al. Alternative splicing determines the intracellular localization of the novel nuclear protein Nop30 and its interaction with the splicing factor SRp30c. — J. Biol. Chem. (1999)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Martin J. et al. The sequence and analysis of duplication-rich human chromosome 16. — Nature (2004)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Gustafsson A.B. et al. Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation. — J. Biol. Chem. (2004)
• Jo D.G. et al. Calcium binding of ARC mediates regulation of caspase 8 and cell death. — Mol. Cell. Biol. (2004)