NOP53

Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis. In ribosome biogenesis, may also play a role in rRNA transcription. 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. 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. 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.

Full Name

NOP53 Ribosome Biogenesis Factor

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.