Molecule Information

General Information of the Molecule (ID: Mol04298)

• Name: Nucleolar protein 3 (NOL3) ,Homo sapiens
• Synonyms: Apoptosis repressor with CARD ; Muscle-enriched cytoplasmic protein ; Nucleolar protein of 30 kDa
• Molecule Type: Protein
• Gene Name: NOL3
• Gene ID: 8996
• Sequence:
  MGNAQERPSETIDRERKRLVETLQADSGLLLDALLARGVLTGPEYEALDALPDAERRVRR
  LLLLVQGKGEAACQELLRCAQRTAGAPDPAWDWQHVGPGYRDRSYDPPCPGHWTPEAPG
  S GTTCPGLPRASDPDEAGGPEGSEAVQSGTPEEPEPELEAEASKEAEPEPEPEPELEPE
  AE AEPEPELEPEPDPEPEPDFEERDESEDS
• Function: [Isoform 1]: May be involved in RNA splicing.{ECO:0000269|PubMed:10196175}.; [Isoform 2]: Functions as an apoptosis repressor that blocksmultiple modes of cell death. Inhibits extrinsic apoptotic pathwaysthrough two different ways. Firstly by interacting with FAS and FADDupon FAS activation blocking death-inducing signaling complex assembly . Secondly by interacting with CASP8 in amitochondria localization- and phosphorylation-dependent manner,limiting the amount of soluble CASP8 available for DISC-mediatedactivation . Inhibits intrinsic apoptotic pathway inresponse to a wide range of stresses, through its interaction with BAXresulting in BAX inactivation, preventing mitochondrial dysfunction andrelease of pro-apoptotic factors . Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer,dissociating its interaction with CASP8 and maintaining calciumhomeostasis . Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of themitochondria-mediated intrinsic pathway, by blocking CASP2 activationand BAX translocation . Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome cfrom mitochondria in a caspase-independent manner . Alsoinhibits TNF-induced necrosis by preventing TNF-signaling pathwaythrough TNFRSF1A interaction abrogating the recruitment of RIPK1 tocomplex I . Finally through its role as apoptosisrepressor, promotes vascular remodeling through inhibition of apoptosisand stimulation of proliferation, in response to hypoxia . Inhibits too myoblast differentiation through caspaseinhibition . {ECO:0000250|UniProtKB:Q62881,ECO:0000250|UniProtKB:Q9D1X0, ECO:0000269|PubMed:15004034,ECO:0000269|PubMed:15509781}.
• Uniprot ID: NOL3_HUMAN
• Ensembl ID: ENSG0000014093915
• HGNC ID: HGNC:7869

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Arsenic trioxide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Acute promyelocytic leukemia [ICD-11: 2A60.2] [1]

• Resistant Disease: Acute promyelocytic leukemia [ICD-11: 2A60.2]
• Resistant Drug: Arsenic trioxide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NB4 cells; Bone marrow; Homo sapiens (Human); CVCL_0005
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: ATO-resistant APL cells showed upregulation of?APAF1,?BCL2,?BIRC3, and?NOL3?genes, while?CD70?and?IL10?genes were downregulated, compared to ATO-sensitive cells.

References

• Ref 1: Combination Treatment of Resistant Acute Promyelocytic Leukemia Cells with Arsenic Trioxide and Anti-Apoptotic Gene Inhibitors. Pharmaceuticals (Basel). 2024 Nov 14;17(11):1529.