NOP53
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 RIGI (PubMed:27824081).
Post-translational modifications
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.
Sequence Similarities
Belongs to the NOP53 family.
Tissue Specificity
Expressed at high levels in heart and pancreas, moderate levels in placenta, liver, skeletal muscle, and kidney, and low levels in brain and lung.
Cellular localization
- Nucleus
- Nucleolus
- Nucleus
- 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:26903295, PubMed:27323397). Also detected in the cytosol (PubMed:24923447, PubMed:27824081).
Alternative names
GLT, GLTSCR2, PICT1, NOP53, Ribosome biogenesis protein NOP53, Glioma tumor suppressor candidate region gene 2 protein, Protein interacting with carboxyl terminus 1, p60, PICT-1