GLTSCR2

Full Name

glioma tumor suppressor candidate region gene 2

Function

Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis (PubMed:24120868).

In ribosome biogenesis, may also play a role in rRNA transcription (PubMed:27729611).

Also functions as a nucleolar sensor that regulates the activation of p53/TP53 in response to ribosome biogenesis perturbation, DNA damage and other stress conditions (PubMed:21741933, PubMed:24120868, PubMed:27829214).

DNA damage or perturbation of ribosome biogenesis disrupt the interaction between NOP53 and RPL11 allowing RPL11 transport to the nucleoplasm where it can inhibit MDM2 and allow p53/TP53 activation (PubMed:24120868, PubMed:27829214).

It may also positively regulate the function of p53/TP53 in cell cycle arrest and apoptosis through direct interaction, preventing its MDM2-dependent ubiquitin-mediated proteasomal degradation (PubMed:22522597).

Originally identified as a tumor suppressor, it may also play a role in cell proliferation and apoptosis by positively regulating the stability of PTEN, thereby antagonizing the PI3K-AKT/PKB signaling pathway (PubMed:15355975, PubMed:16971513, PubMed:27729611).

May also inhibit cell proliferation and increase apoptosis through its interaction with NF2 (PubMed:21167305).

May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation (PubMed:25818168).

Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex (PubMed:25956029).

May also regulate cellular aerobic respiration (PubMed:24556985).

In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of DDX58/RIG-1 (PubMed:27824081).

Biological Process

Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to hypoxia Source: UniProtKB
DNA repair Source: UniProtKB
Mitotic G2 DNA damage checkpoint signaling Source: UniProtKB
Negative regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Negative regulation of protein-containing complex assembly Source: UniProtKB
Negative regulation of protein kinase B signaling Source: UniProtKB
Negative regulation of signal transduction by p53 class mediator Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Negative regulation of transcription of nucleolar large rRNA by RNA polymerase I Source: UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Positive regulation of protein K63-linked deubiquitination Source: UniProtKB
Protein localization to nucleolus Source: Ensembl
Protein localization to nucleoplasm Source: UniProtKB
Protein stabilization Source: UniProtKB
Regulation of aerobic respiration Source: UniProtKB
Regulation of apoptotic process Source: UniProtKB
Regulation of cell cycle Source: UniProtKB
Regulation of protein phosphorylation Source: UniProtKB
Regulation of RIG-I signaling pathway Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: UniProtKB
Ribosomal large subunit assembly Source: HGNC
rRNA processing Source: GO_Central

Cellular Location

Nucleolus; Nucleoplasm. In the nucleolus may be more specifically localized to the fibrillar center (PubMed:27729611). Mainly nucleolar it relocalizes to the nucleoplasm under specific conditions including ribosomal stress enabling it to interact and regulate nucleoplasmic proteins like p53/TP53 (PubMed:22522597, PubMed:24923447, PubMed:27323397, PubMed:26903295). Also detected in the cytosol (PubMed:24923447, PubMed:27824081).

PTM

Ubiquitin-mediated proteasomal degradation is regulated by c-JUN. It is associated with relocalization to the nucleoplasm and decreased homooligomerization.
Phosphorylated upon DNA damage probably by ATM and DNA-PK; may regulate NOP53 degradation.