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Showing NOP53 — PICT1 is a alias.

NOP53

Ribosome biogenesis protein NOP53 · UniProt Q9NZM5

Length
478 aa
Mass
54.4 kDa
Annotated
2026-06-10
48 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOP53 (PICT1/GLTSCR2) is a nucleolar protein that couples 60S ribosome biogenesis to the surveillance pathways that govern cell proliferation, p53 stabilization, and innate immunity (PMID:21804542, PMID:36403484). In its core biogenesis role it acts as an adaptor that recruits the MTR4-RNA exosome to pre-60S particles through an arch-interacting motif (AIM) recognized by the KOW domain of MTR4, directing late ITS2/pre-rRNA processing to mature 5.8S rRNA, and it additionally serves a structural role in pre-60S maturation (PMID:28883156, PMID:31662437, PMID:34125911, PMID:36403484). NOP53 governs the nucleolar stress response: under ribosomal or genotoxic stress it redistributes from nucleolus to nucleoplasm and is degraded — either by ubiquitin-independent 20S proteasomal turnover that requires nucleolar localization (PMID:24923447) or, during DNA damage, following ATM-mediated phosphorylation (PMID:27829214) — releasing RPL11 to inhibit MDM2 and stabilize p53, driving G1 arrest and apoptosis (PMID:21804542, PMID:24045667). NOP53 also stabilizes p53 directly by binding it in the nucleoplasm independently of ARF (PMID:22522597), and disruption of its biogenesis function (loss of NOP53 or MTR4) is sufficient to trigger p53 accumulation, linking ribosome assembly to checkpoint signaling (PMID:36403484). Beyond p53, NOP53 stabilizes PTEN to restrain PI3K/AKT signaling (PMID:16971513), antagonizes the oncogenic NPM-MYC transcriptional axis (PMID:25956029, PMID:25818168), and suppresses autophagy via ZKSCAN3 transcriptional control and histone H3-S10 dephosphorylation (PMID:34502226). Its assembly into the nucleolus is mediated by two nucleolar localization sequences and self-oligomerization through its C-terminal domain (PMID:22292050, PMID:24735870), and it concentrates into nucleolar condensates by liquid-liquid phase separation driven by IDR1 (PMID:36316314). During viral infection NOP53 is exported to the cytoplasm, where it promotes USP15-mediated deubiquitination of RIG-I to attenuate IFN-β signaling (PMID:27824081) and assists HSV-1 γ34.5 in recruiting PP1α to dephosphorylate eIF2α for viral translation (PMID:29367603).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2006 High

    Established a first molecular function for NOP53 outside the nucleolus by showing it binds and stabilizes the PTEN tumor suppressor, linking it to growth-suppressive PI3K/AKT control.

    Evidence RNAi knockdown with PIP3 signaling readouts and PTEN-null isogenic controls in cultured cells

    PMID:16971513

    Open questions at the time
    • Did not define the structural basis or domain of the NOP53-PTEN interaction
    • Did not connect PTEN stabilization to the later-defined nucleolar/ribosome biogenesis role
  2. 2007 Medium

    Showed NOP53 overexpression drives caspase-independent, PTEN-modulated cell death distinct from its effect on PTEN phosphorylation, indicating divergent pro-death activities.

    Evidence Overexpression with cell death and caspase activity assays

    PMID:17657248

    Open questions at the time
    • Death pathway not molecularly resolved
    • Single lab, overexpression-based
  3. 2011 High

    Defined the central nucleolar-stress mechanism: NOP53 retains RPL11 in the nucleolus, and its loss releases RPL11 to inhibit MDM2 and stabilize p53, triggering arrest/apoptosis without DNA damage.

    Evidence Pict1 knockout mouse/ES cells, reciprocal Co-IP, rescue, cell cycle and apoptosis assays

    PMID:21804542

    Open questions at the time
    • Did not address how RPL11 retention is regulated mechanistically
    • Left open the link between RPL11 retention and ribosome biogenesis
  4. 2011 Medium

    Implicated NOP53 in the DNA damage response, showing its loss blunts DDR kinase signaling and abolishes the G2/M checkpoint.

    Evidence shRNA knockdown with γH2AX foci, DDR kinase phosphorylation western blots, and checkpoint analysis

    PMID:21741933

    Open questions at the time
    • Did not establish whether NOP53 acts directly on DDR kinases
    • Single lab, correlative phosphorylation readouts
  5. 2012 Medium

    Demonstrated NOP53 also stabilizes p53 directly by binding it in the nucleoplasm under ribosomal stress, defining an ARF-independent arm of p53 control.

    Evidence Co-IP, subcellular fractionation, ARF-null cell experiments, xenograft model

    PMID:22522597

    Open questions at the time
    • Did not reconcile direct p53 binding with the RPL11-MDM2 mechanism
    • Stoichiometry and binding interface undefined
  6. 2012 Medium

    Mapped the determinants of NOP53 nucleolar targeting to two independent, non-redundant nucleolar localization sequences.

    Evidence Confocal imaging of tagged fusions with systematic NoLS deletion/mutation

    PMID:22292050

    Open questions at the time
    • Did not identify the nucleolar binding partners read by the NoLS
    • No link to stress-induced relocalization
  7. 2013 Medium

    Extended the RPL11-p53 mechanism to a cancer context, showing NOP53 loss in gastric cancer cells displaces RPL11 and triggers TP53-dependent arrest.

    Evidence shRNA knockdown with RPL11 immunofluorescence, colony formation, cell cycle analysis

    PMID:24045667

    Open questions at the time
    • Did not test the pathway in patient tumors mechanistically
    • Single lab
  8. 2014 High

    Revealed how NOP53 protein levels are controlled under nucleolar stress: ubiquitin-independent 20S proteasomal degradation that requires nucleolar localization.

    Evidence Proteasome/E1 inhibitors, in vitro 20S degradation of purified protein, nucleoplasmic localization mutant

    PMID:24923447

    Open questions at the time
    • Did not identify the structural feature licensing 20S recognition
    • Relationship to ubiquitin-dependent degradation routes unresolved
  9. 2014 Medium

    Connected NOP53 to mitochondrial function and Myc-driven metabolism, showing it is required to maintain respiration.

    Evidence Overexpression screen, RNAi in C. elegans respiration assay, Myc target analysis

    PMID:24556985

    Open questions at the time
    • Mechanistic link between NOP53 and Myc left undefined
    • Mitochondrial role not localized to a NOP53 molecular activity
  10. 2014 High

    Showed NOP53 self-associates via its C-terminal domain to form homo-oligomers, defining a structural property relevant to its assembly and regulation.

    Evidence Yeast two-hybrid, Co-IP, FRET, in vitro microfluidic affinity, cross-linking/gel filtration

    PMID:24735870

    Open questions at the time
    • Functional consequence of oligomerization for biogenesis not directly tested here
    • Higher-order assembly state ambiguous
  11. 2015 Medium

    Identified an anti-oncogenic transcriptional function: nucleoplasmic NOP53 competes with MYC for NPM, suppressing NPM-MYC target gene activation and transformation.

    Evidence Co-IP, ChIP, luciferase reporter, anchorage-independent growth assay

    PMID:25956029

    Open questions at the time
    • Did not establish in vivo relevance of NPM competition
    • Single lab
  12. 2015 Medium

    Showed NOP53 additionally promotes proteasomal, ubiquitination-dependent degradation of NPM, reinforcing its suppression of NPM-driven transformation.

    Evidence Co-IP, ubiquitination assay, proteasome inhibitor experiments, soft agar assay

    PMID:25818168

    Open questions at the time
    • E3 ligase for NPM not identified
    • Relationship to the competitive NPM-MYC mechanism unresolved
  13. 2016 Medium

    Defined the DNA-damage trigger for NOP53 turnover: ATM phosphorylates NOP53 (S233/T289), driving its proteasomal degradation and RPL11 release to stabilize p53.

    Evidence Co-IP, phospho-site mutagenesis, kinase inhibitors, RPL11 localization by IF

    PMID:27829214

    Open questions at the time
    • Did not reconcile with the ubiquitin-independent 20S degradation route
    • Direct ATM kinase assay on NOP53 not shown
  14. 2016 Medium

    Linked an upstream kinase signal to NOP53 localization, showing JNK/c-Jun activity maintains nucleolar NOP53 by sustaining monomer-monomer binding, with inhibition causing translocation and degradation.

    Evidence Kinase inhibitor screen, immunocytochemistry, cycloheximide chase, ubiquitination and oligomer Co-IP

    PMID:26903295

    Open questions at the time
    • Mechanism partly inferred from pharmacology
    • Direct JNK target site on NOP53 not mapped
  15. 2016 Medium

    Added a transcription-coupled autophagy arm, showing NOP53 binds rDNA and UBF to repress Pol I recruitment and rRNA transcription, inactivating AKT/mTOR and inducing pro-death autophagy.

    Evidence ChIP on rDNA, Co-IP with UBF, truncation mutants, signaling western blots, autophagy assays

    PMID:27729611

    Open questions at the time
    • Overexpression-driven phenotype
    • Relationship to its exosome-recruitment biogenesis role not addressed
  16. 2016 Medium

    Established a viral immune-evasion function: cytoplasmic NOP53 bridges RIG-I and USP15 to remove K63-ubiquitin from RIG-I, dampening IFN-β and aiding viral replication.

    Evidence Co-IP, NES deletion mutant, IFN-β reporter, ubiquitination and viral replication assays

    PMID:27824081

    Open questions at the time
    • What signals NOP53 nuclear export during infection not defined
    • Single lab
  17. 2017 High

    Resolved the structural basis of NOP53-exosome recruitment, showing the MTR4 KOW domain recognizes the NOP53 AIM and can simultaneously engage AIM protein and RNA.

    Evidence 3.2 Å X-ray crystallography of Mtr4-AIM, NMR, structure-function mutagenesis (yeast)

    PMID:28883156

    Open questions at the time
    • Structure determined for yeast orthologs
    • Did not capture the full pre-60S context of the interaction
  18. 2017 Medium

    Showed NOP53 promotes ARF translocation and ULF/TRIP12-dependent degradation, adding another node by which NOP53 shapes the p53 regulatory network.

    Evidence Co-IP, ARF localization microscopy, ubiquitination assay

    PMID:27323397

    Open questions at the time
    • Reconciliation with NOP53's ARF-independent p53 stabilization unresolved
    • Single lab
  19. 2018 Medium

    Defined a second viral mechanism, with cytoplasmic NOP53 enabling HSV-1 γ34.5 recruitment of PP1α to dephosphorylate eIF2α and sustain viral translation.

    Evidence Co-IP, eIF2α phosphorylation western blot, viral yield assays, mouse infection model

    PMID:29367603

    Open questions at the time
    • Whether the same export pathway is used as in RIG-I attenuation not tested
    • Host consequence in uninfected cells unclear
  20. 2019 Medium

    Established NOP53 as the adaptor that times RNA exosome association with pre-60S particles, interacting with Rrp6, Mtr4 and 25S rRNA to drive 7S→5.8S processing.

    Evidence Proteomic interactome, Co-IP, pre-rRNA processing assays in yeast

    PMID:31662437

    Open questions at the time
    • Yeast ortholog; human relevance addressed only later
    • Did not separate structural from adaptor roles
  21. 2021 Medium

    Distinguished NOP53's structural role from its exosome-recruitment role, showing it replaces Erb1 at the pre-60S foot and that the AIM is needed specifically for late ITS2 processing.

    Evidence Yeast genetics (depletion vs AIM mutants), cryo-EM-informed biochemistry, northern blot, proteomics

    PMID:34125911

    Open questions at the time
    • Mechanism of the nucleolar-to-nuclear transition not fully defined
    • Yeast system
  22. 2021 Medium

    Detailed the autophagy-suppressive program of NOP53 via ZKSCAN3 transcriptional activation and H3-S10 dephosphorylation to downregulate ATG7/ATG12.

    Evidence Co-IP with H3, ChIP, luciferase reporter, siRNA, autophagy flux assays

    PMID:34502226

    Open questions at the time
    • The phosphatase activity/recruitment for H3-S10 not identified
    • Reconciliation with pro-death autophagy report (#15) unaddressed
  23. 2022 Medium

    Translated the exosome-adaptor role to human cells, showing PICT1 acts at two pre-rRNA steps and that loss of its biogenesis function (or MTR4) stabilizes p53, mechanistically linking ribosome assembly to nucleolar stress signaling.

    Evidence Co-IP, AIM mutant, siRNA knockdown, northern blot, p53 western blot

    PMID:36403484

    Open questions at the time
    • Did not separate which biogenesis defect activates p53
    • Single lab
  24. 2022 Medium

    Showed NOP53 undergoes IDR1-driven liquid-liquid phase separation, separable from M-R motif-dependent nucleolar localization, providing a biophysical basis for its nucleolar concentration.

    Evidence LLPS droplet assays (FRAP, fusion, hexanediol), IDR1 and M-R motif mutants, p53 pathway readouts

    PMID:36316314

    Open questions at the time
    • Functional consequence of LLPS for ribosome biogenesis not directly demonstrated
    • Single lab
  25. 2024 Medium

    Identified a NOP53-MRE11 interaction in alveolar type II cells, linking NOP53 to ROS control, mitochondrial respiration, and DNA repair after cigarette smoke exposure.

    Evidence Co-IP/MS, PICT1 deletion cell model, ROS and mitochondrial respiration assays, DNA damage assays

    PMID:39578839

    Open questions at the time
    • Direct functional role of the MRE11 interaction in repair not dissected
    • Single lab, single cell context

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how NOP53's multiple regulatory outputs — exosome-coupled 60S biogenesis, p53/RPL11 stress signaling, NPM-MYC and PTEN control, autophagy suppression, and cytoplasmic immune modulation — are integrated and switched, including which degradation route and relocalization signal dominates under each stress.
  • No unified model linking biogenesis defects to specific downstream effector arms
  • The signal hierarchy controlling nucleolar retention vs export vs degradation is undefined
  • Human structural data for the pre-60S role is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2 GO:0003677 DNA binding 1 GO:0003723 RNA binding 1 GO:0042393 histone binding 1
Localization
GO:0005654 nucleoplasm 3 GO:0005730 nucleolus 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
MRE11MTR4NPM1PTENRPL11RRP6TP53USP15
Complex memberships
RNA exosome (pre-60S adaptor)pre-60S ribosomal particle

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 PICT1/NOP53 binds RPL11 in the nucleolus, retaining it there; loss of PICT1 releases RPL11 to the nucleoplasm where it binds MDM2, blocking MDM2-mediated ubiquitination of p53 and causing p53 accumulation and G1 arrest/apoptosis even without DNA damage. Pict1 knockout mouse/ES cells, Co-IP, cell cycle analysis, apoptosis assays, rescue experiments Nature Medicine High 21804542
2006 PICT-1/NOP53 binds and stabilizes PTEN protein; RNAi knockdown of PICT-1 decreases endogenous PTEN, activates downstream PI3K/Akt signaling, promotes proliferation and anchorage-independent growth in a PTEN-dependent manner. RNAi knockdown, western blot, PIP3 signaling assays, soft-agar colony formation, PTEN-null cell controls Molecular Biology of the Cell High 16971513
2007 GLTSCR2/NOP53 overexpression induces caspase-independent, PTEN-modulated apoptotic cell death; this cytotoxic activity is independent of its ability to phosphorylate PTEN, indicating a divergent cell death pathway. Overexpression, cell death assays, caspase activity assays, PTEN phosphorylation assays Cell Death and Differentiation Medium 17657248
2012 GLTSCR2/NOP53 translocates from nucleolus to nucleoplasm under ribosomal stress, where it directly interacts with and stabilizes p53, inhibiting cell cycle progression independently of ARF. Co-IP, subcellular fractionation/immunofluorescence, ARF-null cell experiments, xenograft model Cell Death and Differentiation Medium 22522597
2017 Crystal structure (3.2 Å) of S. cerevisiae Mtr4 bound to the arch-interacting motif (AIM) of Nop53 reveals that the KOW domain of Mtr4 recognizes AIM via hydrophobic and electrostatic interactions; NMR shows the KOW domain can simultaneously bind an AIM protein and structured RNA at adjacent surfaces. X-ray crystallography (3.2 Å), NMR, structure-function mutagenesis RNA High 28883156
2011 GLTSCR2/NOP53 is involved in the DNA damage response; knockdown attenuates phospho-H2AX foci formation and phosphorylation of ATM, ATR, Chk1, Chk2, and H2AX, sensitizes cells to DNA damage, delays DNA repair, and abolishes G2/M checkpoint activation. shRNA knockdown, immunofluorescence (γH2AX foci), western blot for DDR kinases, DNA repair assays, checkpoint analysis The American Journal of Pathology Medium 21741933
2014 Nucleolar stress inducers (actinomycin D, 5-fluorouridine, doxorubicin) cause proteasome-mediated degradation of PICT1/NOP53 in a ubiquitin-independent manner; the 20S proteasome degrades purified PICT1 in vitro; nucleolar localization is required for stress-induced degradation in cells. Proteasome inhibitors, E1 ubiquitin-activating enzyme inhibitor, genetic inactivation, in vitro 20S proteasome degradation assay, nucleoplasmic localization mutant The Journal of Biological Chemistry High 24923447
2009 PICT-1/NOP53 interacts with the KSHV anti-apoptotic protein KS-Bcl-2; ectopic PICT-1 expression dramatically increases nucleolar localization of KS-Bcl-2 and reduces its antiapoptotic activity, while PICT-1 knockdown abolishes nucleolar targeting of KS-Bcl-2. Yeast two-hybrid screen, Co-IP, confocal microscopy, siRNA knockdown, domain mapping Journal of Virology Medium 20042497
2010 Ser518-dephosphorylated (growth-inhibitory) merlin interacts with PICT-1/NOP53 in the nucleolus; PICT-1 overexpression represses cyclin D1, arrests the cell cycle at G0/G1, and promotes apoptosis; a PICT-1 C-terminal truncation mutant lacking merlin-binding has reduced growth-inhibitory effects, and merlin siRNA attenuates PICT-1-induced growth inhibition. Co-IP, confocal microscopy, dominant-negative/truncation mutants, siRNA, cell cycle analysis, cyclin D1 western blot The International Journal of Biochemistry & Cell Biology Medium 21167305
2012 Nucleolar localization of PICT-1/NOP53 is mediated by two independent nucleolar localization sequences (NoLS), which are relatively long, contain arginine and leucine clusters, and have flexible boundaries; neither NoLS is sufficient alone to direct full nucleolar targeting. Confocal microscopy of EGFP/myc-tagged fusion proteins, deletion/mutation analysis of NoLS PLoS ONE Medium 22292050
2014 PICT-1/NOP53 self-associates to form homo-oligomers (primarily dimers, possibly higher-order), mediated by the carboxy-terminal domain, as shown by yeast two-hybrid, Co-IP, FRET in mammalian cells, in vitro microfluidic affinity assays, and glutaraldehyde cross-linking/gel filtration. Yeast two-hybrid, Co-IP, FRET, in vitro microfluidic affinity binding, glutaraldehyde cross-linking, gel filtration Journal of Molecular Biology High 24735870
2015 GLTSCR2/NOP53 redistributes from nucleolus to nucleoplasm where increased GLTSCR2-NPM interaction competitively inhibits NPM-MYC binary complex formation, reducing recruitment of NPM-MYC to MYC target gene promoters and suppressing MYC transcriptional and transformational activity. Co-IP, ChIP, luciferase reporter assay, anchorage-independent growth assay, confocal microscopy The American Journal of Pathology Medium 25956029
2015 GLTSCR2/NOP53 induces nucleoplasmic translocation and proteasomal polyubiquitination-dependent degradation of nucleophosmin (NPM); this decreases NPM-driven cellular transformation. Co-IP, confocal microscopy, proteasome inhibitor experiments, ubiquitination assay, soft agar assay Journal of Cellular and Molecular Medicine Medium 25818168
2016 During DNA damage, PICT-1/NOP53 is phosphorylated by ATM (at S233 and T289), then undergoes proteasomal degradation; loss of PICT-1 releases RPL11 from the nucleolus, increasing RPL11-MDM2 binding and promoting p53 accumulation. ATM co-localizes and interacts with PICT-1 in the nucleolus. Co-IP (ATM-PICT1, Ku70-PICT1), anti-phospho-substrate antibody, site-directed mutagenesis (S233A/T289A and phosphomimetic S233D/T289D), kinase inhibitors (wortmannin, KU55933), RPL11 localization by IF Oncotarget Medium 27829214
2016 During viral infection (VSV, HSV-1), NOP53/GLTSCR2 translocates from nucleus to cytoplasm where it interacts with RIG-I and USP15; the triple interaction activates USP15 to remove K63-linked ubiquitination from RIG-I, attenuating RIG-I signaling and IFN-β production to support viral replication. Deletion of the NES of NOP53 abrogates this function. Co-IP (NOP53-RIG-I, NOP53-USP15), NES deletion mutant, IFN-β reporter assay, viral replication assays, ubiquitination assay Scientific Reports Medium 27824081
2016 PICT-1/NOP53 overexpression triggers pro-death autophagy by directly binding ribosomal DNA (rDNA) and interacting with UBF, inhibiting UBF phosphorylation and Pol I recruitment to the rDNA promoter, thereby suppressing rRNA transcription and inactivating the AKT/mTOR/p70S6K signaling pathway. ChIP (PICT-1 on rDNA), Co-IP (PICT-1-UBF), truncation mutants, Pol I ChIP, AKT/mTOR signaling western blot, autophagy assays Oncotarget Medium 27729611
2016 JNK activity (via phosphorylation of c-Jun) is required to maintain nucleolar localization of GLTSCR2/NOP53; inhibition of JNK by SP600125 or c-Jun peptide causes nucleoplasmic translocation of GLTSCR2 and its degradation via the proteasome-polyubiquitination pathway, mediated by reduced GLTSCR2 monomer-monomer binding affinity. Protein kinase inhibitor screen, immunocytochemistry, cycloheximide chase, ubiquitination assay, Co-IP (oligomer status) Biochemical and Biophysical Research Communications Medium 26903295
2017 GLTSCR2/NOP53 binds ARF in the nucleolus and promotes ARF translocation to the nucleoplasm where it increases ARF binding to the E3 ubiquitin ligase ULF/TRIP12, enhancing ARF polyubiquitination and degradation. Co-IP (GLTSCR2-ARF, ARF-ULF), confocal microscopy (ARF localization), ubiquitination assay Oncotarget Medium 27323397
2018 NOP53/GLTSCR2 translocates to the cytoplasm during HSV-1 infection driven by viral protein γ34.5; cytoplasmic NOP53 facilitates γ34.5 recruitment of protein phosphatase PP1α to dephosphorylate eIF2α, enabling efficient viral protein translation. NOP53 knockdown impairs the γ34.5-PP1α interaction and reduces viral virulence in vivo. Co-IP (NOP53-γ34.5, γ34.5-PP1α), eIF2α phosphorylation western blot, viral yield assays, in vitro expression, mouse infection model Cell Death & Disease Medium 29367603
2019 Yeast Nop53 controls when the RNA exosome associates with pre-60S particles; Nop53 interacts with the exosome catalytic subunit Rrp6, Mtr4, and 25S rRNA and acts as an adaptor recruiting the exosome for 7S pre-rRNA processing to 5.8S rRNA. Proteomic analysis suggests Nop53 also positions the exosome during 7S processing. Proteomics-based interactome analysis (MS), Co-IP (Nop53-Rrp6, Nop53-Mtr4), pre-rRNA processing assays in yeast The Journal of Biological Chemistry Medium 31662437
2021 Yeast Nop53 has a structural role in pre-60S maturation: it replaces Erb1 at the foot of the pre-60S particle, and its depletion (not just AIM mutants) blocks transition from nucleolar state E particle to nuclear stages and impairs late maturation events including Yvh1 recruitment. The AIM-exosome interaction is required specifically for late (not early) ITS2 processing. Yeast genetics (depletion, AIM mutants), cryo-EM-informed biochemical analysis, northern blot (pre-rRNA intermediates), proteomics Nucleic Acids Research Medium 34125911
2021 NOP53 suppresses autophagy through two pathways: (1) transcriptional activation of the master autophagy suppressor ZKSCAN3, inhibiting LC3B induction; and (2) physical interaction with histone H3 to dephosphorylate H3-S10, transcriptionally downregulating ATG7 and ATG12 expression. Co-IP (NOP53-H3), ChIP, luciferase reporter, siRNA knockdown, autophagy flux assays (LC3B, ATG7, ATG12 western blot) International Journal of Molecular Sciences Medium 34502226
2022 Human PICT1/NOP53 interacts with MTR4 and the RNA exosome via an AIM sequence and is involved in two distinct pre-rRNA processing steps during 60S biogenesis: early cleavage of 32S intermediate RNA and late maturation of 12S precursor to 5.8S rRNA. AIM-dependent MTR4/exosome recruitment is required only for the late step. PICT1 or MTR4 depletion (but not exosome catalytic subunit depletion) stabilizes p53, linking the ribosome biogenesis function to nucleolar stress signaling. Co-IP (PICT1-MTR4, PICT1-exosome), AIM mutant overexpression, siRNA knockdown, northern blot (pre-rRNA intermediates), p53 western blot Biochemical and Biophysical Research Communications Medium 36403484
2022 NOP53 undergoes liquid-liquid phase separation (LLPS) in vitro and in vivo; its intrinsically disordered region 1 (IDR1) is required for phase separation, while multivalent arginine-rich linear motifs (M-R motifs) are required for nucleolar localization but dispensable for LLPS. NOP53 negatively regulates the p53 pathway in colorectal cancer cells with or without radiation. LLPS droplet assays (fusion, FRAP, 1,6-hexanediol sensitivity), IDR1 deletion mutant, M-R motif mutant, confocal microscopy, p53 pathway western blot, clonogenic survival assay Cell Death Discovery Medium 36316314
2024 PICT1/NOP53 interacts with MRE11 (a DNA damage repair factor) in alveolar type II cells; PICT1 deletion leads to increased ROS, mitochondrial dysfunction, impaired mitochondrial respiration, and impaired DNA damage repair following cigarette smoke extract exposure. Co-IP followed by mass spectrometry (identified MRE11 as novel PICT1 interactor), PICT1 deletion cell model, ROS assay, mitochondrial respiration assay, DNA damage assays Cell Communication and Signaling Medium 39578839
2014 GLTSCR2/PICT1 enhances mitochondrial function and is required for maintenance of oxygen consumption; its inactivation in C. elegans reduces respiration. GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc and is induced by mitochondrial stress. High-throughput overexpression screen (flow cytometry), RNAi in C. elegans (respiration assay), Myc target gene analysis PNAS Medium 24556985
2013 PICT1/NOP53 loss in gastric cancer cells causes RPL11 translocation out of the nucleolus, impairing cell proliferation and colony formation via TP53-mediated cell cycle arrest. shRNA knockdown, RPL11 immunofluorescence (localization), colony formation assay, cell cycle analysis British Journal of Cancer Medium 24045667

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nature medicine 153 21804542
2006 Critical role of PICT-1, a tumor suppressor candidate, in phosphatidylinositol 3,4,5-trisphosphate signals and tumorigenic transformation. Molecular biology of the cell 72 16971513
2007 The putative tumor suppressor gene GLTSCR2 induces PTEN-modulated cell death. Cell death and differentiation 62 17657248
2012 Nucleolar protein GLTSCR2 stabilizes p53 in response to ribosomal stresses. Cell death and differentiation 57 22522597
2008 Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas. The Journal of pathology 47 18729076
2017 Structural insights into the interaction of the nuclear exosome helicase Mtr4 with the preribosomal protein Nop53. RNA (New York, N.Y.) 37 28883156
2011 Involvement of GLTSCR2 in the DNA Damage Response. The American journal of pathology 32 21741933
2013 PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression. British journal of cancer 30 24045667
2018 The pre-rRNA processing factor Nop53 regulates fungal development and pathogenesis via mediating production of reactive oxygen species. Environmental microbiology 27 29488307
2015 The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis. The American journal of pathology 23 25956029
2012 Nucleolar localization of GLTSCR2/PICT-1 is mediated by multiple unique nucleolar localization sequences. PloS one 22 22292050
2019 NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer. Genes 20 31703244
2016 PICT-1 triggers a pro-death autophagy through inhibiting rRNA transcription and AKT/mTOR/p70S6K signaling pathway. Oncotarget 20 27729611
2010 Moesin-ezrin-radixin-like protein (merlin) mediates protein interacting with the carboxyl terminus-1 (PICT-1)-induced growth inhibition of glioblastoma cells in the nucleus. The international journal of biochemistry & cell biology 20 21167305
2022 NOP53 undergoes liquid-liquid phase separation and promotes tumor radio-resistance. Cell death discovery 19 36316314
2009 GLTSCR2/PICT-1, a putative tumor suppressor gene product, induces the nucleolar targeting of the Kaposi's sarcoma-associated herpesvirus KS-Bcl-2 protein. Journal of virology 18 20042497
2016 The nucleolar protein GLTSCR2 is required for efficient viral replication. Scientific reports 16 27824081
2014 GLTSCR2/PICT1 links mitochondrial stress and Myc signaling. Proceedings of the National Academy of Sciences of the United States of America 15 24556985
2018 Downregulation of NOP53 Ribosome Biogenesis Factor Leads to Abnormal Nuclear Division and Chromosomal Instability in Human Cervical Cancer Cells. Pathology oncology research : POR 14 30421090
2020 The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response. Cancers 13 32867128
2016 PICT-1 is a key nucleolar sensor in DNA damage response signaling that regulates apoptosis through the RPL11-MDM2-p53 pathway. Oncotarget 13 27829214
2021 PICT1 is critical for regulating the Rps27a-Mdm2-p53 pathway by microtubule polymerization inhibitor against cervical cancer. Biochimica et biophysica acta. Molecular cell research 12 34166715
2018 Multifunctional viral protein γ34.5 manipulates nucleolar protein NOP53 for optimal viral replication of HSV-1. Cell death & disease 12 29367603
2013 Downregulation of GLTSCR2 expression is correlated with breast cancer progression. Pathology, research and practice 12 24054033
2015 GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical cancer. Journal of cellular and molecular medicine 11 25818168
2014 Nucleolar stress induces ubiquitination-independent proteasomal degradation of PICT1 protein. The Journal of biological chemistry 11 24923447
2019 The ribosome assembly factor Nop53 controls association of the RNA exosome with pre-60S particles in yeast. The Journal of biological chemistry 10 31662437
2017 GLTSCR2 promotes the nucleoplasmic translocation and subsequent degradation of nucleolar ARF. Oncotarget 9 27323397
2014 The nucleolar PICT-1/GLTSCR2 protein forms homo-oligomers. Journal of molecular biology 9 24735870
2013 Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53. Annals of surgical oncology 9 23532381
2010 The expression of GLTSCR2, a candidate tumor suppressor, is reduced in seborrheic keratosis compared to normal skin. Pathology, research and practice 9 20185249
2021 The ribosome assembly factor Nop53 has a structural role in the formation of nuclear pre-60S intermediates, affecting late maturation events. Nucleic acids research 8 34125911
2021 NOP53 Suppresses Autophagy through ZKSCAN3-Dependent and -Independent Pathways. International journal of molecular sciences 8 34502226
2017 Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals. Antiviral research 8 28286234
2012 GLTSCR2 contributes to the death resistance and invasiveness of hypoxia-selected cancer cells. FEBS letters 8 22850112
2013 Down-regulation and aberrant cytoplasmic expression of GLTSCR2 in prostatic adenocarcinomas. Cancer letters 6 23920125
2007 GLTSCR2 sensitizes cells to hypoxic injury without involvement of mitochondrial apoptotic cascades. Pathobiology : journal of immunopathology, molecular and cellular biology 6 17890897
2024 Mitochondrial dysfunction and impaired DNA damage repair through PICT1 dysregulation in alveolar type II cells in emphysema. Cell communication and signaling : CCS 5 39578839
2016 c-Jun N-terminal kinase regulates the nucleoplasmic translocation and stability of nucleolar GLTSCR2 protein. Biochemical and biophysical research communications 5 26903295
2013 Expression of GLTSCR2/Pict-1 in squamous cell carcinomas of the skin. Archives of dermatological research 5 23942755
2022 The role of PICT1 in RPL11/Mdm2/p53 pathway-regulated inhibition of cell growth induced by topoisomerase IIα inhibitor against cervical cancer cell line. Biochemical pharmacology 3 35605655
2022 MTR4 adaptor PICT1 functions in two distinct steps during pre-rRNA processing. Biochemical and biophysical research communications 3 36403484
2018 Abnormal Expression of PICT-1 and Its Codon 389 Polymorphism Is a Risk Factor for Human Endometrial Cancer. Oncology 3 29617699
2016 Role of GLTSCR2 in the regulation of telomerase activity and chromosome stability. Molecular medicine reports 3 27357325
2018 Cytoplasmic Translocation of Nucleolar Protein NOP53 Promotes Viral Replication by Suppressing Host Defense. Viruses 2 29677136
2014 The expression of GLTSCR2 in cervical intra-epithelial lesion and cancer. Archives of gynecology and obstetrics 2 25118835
2022 PICT-1 regulates p53 splicing and sensitivity of medullary thyroid carcinoma cells to everolimus. Journal of neuroendocrinology 1 36306198
2015 Suppression of GLTSCR2 expression in renal cell carcinomas. Pathology, research and practice 1 26724143

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