NOL3

This gene encodes an anti-apoptotic protein that has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53.

Full Name

nucleolar protein 3 (apoptosis repressor with CARD domain)

Function

Isoform 1
May be involved in RNA splicing.
Isoform 2
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).

Biological Process

Blood vessel remodelingIEA:Ensembl
Cardiac muscle cell apoptotic processIEA:Ensembl
Inhibition of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Intrinsic apoptotic signaling pathwayIEA:Ensembl
mRNA splice site selectionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cardiac muscle cell apoptotic processIEA:Ensembl
Negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of hypoxia-induced intrinsic apoptotic signaling pathwayISS:UniProtKB
Negative regulation of intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of mitochondrial membrane permeability involved in apoptotic processIEA:Ensembl
Negative regulation of muscle atrophyIEA:Ensembl
Negative regulation of necrotic cell deathIEA:Ensembl
Negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of release of cytochrome c from mitochondriaManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of tumor necrosis factor-mediated signaling pathwayIEA:Ensembl
Protein complex oligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of NIK/NF-kappaB signalingIEA:Ensembl
Release of sequestered calcium ion into cytosol by sarcoplasmic reticulumManual Assertion Based On ExperimentIDA:UniProtKB
Response to hypoxiaIEA:Ensembl
Response to injury involved in regulation of muscle adaptationIEA:Ensembl
Response to ischemiaIEA:Ensembl
RNA splicingManual Assertion Based On ExperimentTAS:ProtInc

Involvement in disease

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.

PTM

Phosphorylation at Thr-149 is required for its antiapoptotic effect by blocking death-inducing signaling complex death-inducing signaling complex (DISC) activity through the control of interaction with CASP8. Phosphorylation at Thr-149 results in translocation to mitochondria and this translocation enables the binding to CASP8. Dephosphorylated at Thr-149 by calcineurin; doesn't inhibit the association between FADD and CASP8 and the consequent apoptosis.
Polyubiquitinated by MDM2; promoting proteasomal-dependent degradation in response to apoptotic stimuli.