Affinage

SSU72

RNA polymerase II subunit A C-terminal domain phosphatase SSU72 · UniProt Q9NP77

Length
194 aa
Mass
22.6 kDa
Annotated
2026-04-28
44 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SSU72 is a conserved dual-specificity phosphatase that couples RNA polymerase II CTD dephosphorylation with transcription initiation, elongation, termination, and pre-mRNA 3'-end processing. It preferentially dephosphorylates Ser5-P and Ser7-P on the RNAP II CTD through a CX5R catalytic cysteine motif structurally related to low-molecular-weight protein tyrosine phosphatases, with strict specificity for the cis-proline configuration of the CTD substrate facilitated by the Pin1/Ess1 prolyl isomerase (PMID:12606538, PMID:21159777, PMID:22235117). As a stable subunit of the cleavage and polyadenylation factor (CPF) complex via its interaction with Pta1/symplekin, SSU72 is required for pre-mRNA 3'-end cleavage and transcription termination of both polyadenylated mRNAs and snoRNAs, while also bridging the transcription initiation machinery through interactions with TFIIB and RNAP II (PMID:12453421, PMID:12704082, PMID:20861839). Beyond its nuclear transcriptional roles, SSU72 functions as a tyrosine phosphatase for ZAP-70 in TCR signaling, dephosphorylates eIF2α to regulate translational control of thermogenesis in brown adipose tissue, controls telomere replication by dephosphorylating Stn1, and regulates GM-CSF receptor signaling in macrophages (PMID:34452999, PMID:36841836, PMID:30796050, PMID:32910932).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    The discovery that SSU72 is an essential gene functionally linked to TFIIB in transcription start site selection established it as a core component of the basal transcription machinery, before its enzymatic activity was known.

    Evidence Genetic suppressor analysis and in vivo start site mapping in yeast

    PMID:8657130

    Open questions at the time
    • No biochemical activity assigned
    • Mechanism of start site selection influence unknown
    • No physical interaction demonstrated
  2. 2000 High

    Demonstration that Ssu72 physically contacts RNAP II via the Rpb2 subunit shifted the model from purely genetic interaction to direct engagement with the transcription machinery.

    Evidence Co-immunoprecipitation with purified RNAP II and genetic suppressor (rpb2-100) in yeast

    PMID:11046131

    Open questions at the time
    • Enzymatic activity still unknown
    • Binding surface on Rpb2 not structurally resolved
  3. 2002 High

    Identification of Ssu72 as a stable CPF subunit that bridges 3'-end processing factors (Pta1, Ydh1) to TFIIB and RNAP II unified its roles in transcription and mRNA processing within a single complex.

    Evidence Biochemical fractionation, co-immunoprecipitation, and 6-azauracil genetic suppression in yeast

    PMID:12453421

    Open questions at the time
    • Catalytic function not yet identified
    • Whether transcription and processing roles are separable was unclear
  4. 2003 High

    Three concurrent studies established Ssu72 as a phosphatase with a CX5R active site related to LMWPTPs, demonstrated its requirement for both snoRNA and mRNA transcription termination pathways, and showed it is essential for pre-mRNA 3'-end cleavage — transforming understanding from genetic factor to defined enzyme.

    Evidence In vitro pNPP phosphatase assay with active-site mutagenesis, transcription termination readthrough assays, and in vitro cleavage reconstitution in yeast

    PMID:12606538 PMID:12660165 PMID:12704082 PMID:12944462

    Open questions at the time
    • Physiological substrate not yet identified
    • Whether cleavage role requires catalytic activity unknown
  5. 2004 High

    Identification of CTD Ser5-P as the specific physiological substrate of Ssu72 phosphatase, and demonstration that the 3'-end processing function is catalytic-activity-independent, revealed separable enzymatic and structural roles.

    Evidence In vitro CTD phosphatase assay with depletion/rescue and catalytic mutant analysis in yeast

    PMID:15125841

    Open questions at the time
    • Structural basis of substrate recognition unknown
    • Whether Ssu72 targets additional CTD marks unclear
  6. 2006 High

    Demonstration that Ssu72 catalytic activity controls Ser5-P levels in vivo during the initiation-to-elongation transition, with genetic suppressors encoding slow RNAP II forms, positioned Ssu72 as a kinetic checkpoint facilitating elongation commitment.

    Evidence In vitro phosphatase and transcription elongation assays, in vivo CTD phosphorylation analysis, and genetic suppressor screen in yeast

    PMID:17101794

    Open questions at the time
    • Mechanism of elongation facilitation not structurally resolved
    • Relationship to capping checkpoint not established
  7. 2010 High

    Crystal structures of the symplekin–Ssu72–CTD ternary complex revealed the unprecedented requirement for cis-proline conformation at the Ser5-P–Pro6 bond, and showed that the Pin1/Ess1 prolyl isomerase facilitates Ssu72 activity by generating this substrate conformation.

    Evidence X-ray crystallography (2.4 Å), NMR, in vitro phosphatase kinetics with Pin1/Ess1 isomerization

    PMID:20861839 PMID:21159777

    Open questions at the time
    • How cis-proline specificity arose evolutionarily unclear
    • Full-length CTD substrate conformation unknown
  8. 2012 High

    Discovery that Ssu72 also dephosphorylates Ser7-P on the CTD — albeit with ~4000-fold lower activity than Ser5-P — expanded its substrate repertoire and explained how coupled removal of both marks enables termination and PIC reassembly.

    Evidence Crystal structure of symplekin–Ssu72–pSer7 CTD complex, in vitro phosphatase kinetics, in vivo lethality of Ser7E phospho-mimic

    PMID:22235117 PMID:23070812

    Open questions at the time
    • Physiological relevance of low Ser7-P activity versus other phosphatases unclear
    • Whether Ser7-P dephosphorylation occurs on free or engaged CTD unknown
  9. 2013 High

    Identification of Aurora B kinase as a mitotic regulator that phosphorylates Ssu72 at Ser19, triggering its degradation and inactivation, revealed a non-transcriptional role for Ssu72 in maintaining chromosome arm cohesion.

    Evidence In vitro kinase/phosphatase assays, ubiquitination assay, phosphomimetic overexpression with chromosome cohesion readout in human cells

    PMID:24149858

    Open questions at the time
    • Direct cohesin subunit substrate of Ssu72 not identified
    • Structural basis of Aurora B–Ssu72 interaction unknown
  10. 2019 High

    Discovery that Ssu72 dephosphorylates Stn1 at Ser74 to control telomere lagging-strand synthesis, conserved from fission yeast to human cells, established a third major cellular context (telomere maintenance) for Ssu72 beyond transcription and mitosis.

    Evidence Fission yeast ssu72Δ genetics, telomere ChIP, in vitro phosphatase assay, human siRNA knockdown

    PMID:30796050

    Open questions at the time
    • Kinase responsible for Stn1 Ser74 phosphorylation not identified
    • Mechanism linking Stn1 dephosphorylation to polymerase α–primase recruitment unclear
  11. 2020 Medium

    Demonstration that Pin1 recruits Ssu72 to CTD during oxidative stress-responsive transcription in fission yeast, with extensive transcriptomic overlap between pin1Δ and ssu72 inactivation, placed Pin1 as an obligate upstream activator of Ssu72 in stress signaling.

    Evidence Co-immunoprecipitation, ChIP, transcriptional profiling, genetic epistasis in fission yeast

    PMID:32282918 PMID:33410907

    Open questions at the time
    • Whether Pin1–Ssu72 coupling operates at all gene classes or only stress genes unknown
    • Human cell validation limited
  12. 2021 High

    Identification of ZAP-70 as a direct tyrosine-phosphorylated substrate of Ssu72 in T cells, with AP-MS validation and in vitro dephosphorylation, established Ssu72 as a bona fide tyrosine phosphatase operating in TCR signaling outside the transcription cycle.

    Evidence AP-MS, in vitro phosphatase assay with recombinant proteins, conditional T cell KO with phospho-western blot

    PMID:34452999

    Open questions at the time
    • Specificity for particular ZAP-70 tyrosine residues not mapped
    • Whether Ssu72 tyrosine phosphatase activity uses the same CX5R mechanism as CTD activity not structurally confirmed
  13. 2022 Medium

    Discovery that avian influenza NS1 protein targets SSU72 for degradation, causing transcriptional readthrough that suppresses STAT1/2 innate immune gene expression, revealed SSU72 as a host factor exploited by viral immune evasion.

    Evidence Co-immunoprecipitation (NS1–SSU72), readthrough analysis, mouse lung injury model, SSU72 overexpression rescue

    PMID:35332300

    Open questions at the time
    • Mechanism of NS1-induced SSU72 degradation not defined
    • Whether other viral proteins similarly target SSU72 unknown
  14. 2023 High

    Identification of eIF2α as a direct dephosphorylation target of Ssu72 in brown adipose tissue, controlling translational output of mitochondrial OXPHOS subunits and thermogenesis, extended Ssu72's non-CTD substrate repertoire to translational regulation.

    Evidence Adipocyte-specific conditional KO mouse, polysome profiling, phospho-eIF2α western blot, cold tolerance test, rescue by Ssu72 re-expression

    PMID:36841836

    Open questions at the time
    • Whether Ssu72 dephosphorylates eIF2α directly or via an intermediate not reconstituted with purified components
    • Tissue specificity of this function beyond BAT unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Ssu72 achieves substrate selectivity across its diverse targets (CTD Ser5-P/Ser7-P, ZAP-70 tyrosine phosphorylation, eIF2α, Stn1, cohesin) and whether distinct regulatory inputs (symplekin/Pta1, Pin1, Aurora B) partition Ssu72 activity among these substrates in different cellular compartments remains unresolved.
  • No unified structural model of multi-substrate recognition
  • Compartment-specific regulation not systematically addressed
  • Whether transcriptional and non-transcriptional functions are coordinated or independent is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0098772 molecular function regulator activity 6
Localization
GO:0005634 nucleus 5 GO:0005886 plasma membrane 2
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 2 R-HSA-69306 DNA Replication 1
Partners
CSF2RBPIN1PLCG1RPB2STN1SYMPKTFIIBZAP70
Complex memberships
CPF (cleavage and polyadenylation factor)symplekin–Ssu72 complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 SSU72 was identified as an essential yeast gene encoding a novel protein that functionally interacts with TFIIB (Sua7) to affect transcription start site selection; the ssu72-1 allele (a 30-bp duplication creating a zinc-binding motif) synthetically enhances a TFIIB defect, dramatically shifting start site selection downstream at ADH1, and both SUA7 and SSU72 rescue the phenotype, defining a functional relationship. Genetic epistasis, suppressor analysis, site-directed mutagenesis, in vivo transcription start site mapping Molecular and cellular biology High 8657130
1999 Genetic interactions between ssu72-1 and sub1Δ with sua7 alleles are allele-specific and overlapping, and each sua7 allele that interacts with ssu72 affects transcription start site selection accuracy, demonstrating functional interactions among TFIIB, Ssu72, and Sub1 in the mechanism of start site selection. Genetic epistasis, allele-specific interaction analysis, in vivo transcription assays Genetics Medium 10511545
2000 Ssu72 physically interacts directly with purified RNA polymerase II (via the Rpb2 subunit) as shown by co-immunoprecipitation, and genetic suppressor analysis identified an rpb2-100 allele (R512C in homology block D) as a suppressor of ssu72-2, defining a physical and functional interaction between Ssu72 and the RNAP II core machinery. Co-immunoprecipitation with purified RNAP II, genetic suppressor screen, in vivo transcription assays Molecular and cellular biology High 11046131
2002 Ssu72 is a stable component of yeast CPF (cleavage and polyadenylation factor) and bridges CPF subunits Pta1 and Ydh1/Cft2, the general transcription factor TFIIB, and RNAP II via Rpb2; ssu72-2 mutants show defects in RNAP II transcription elongation and termination, and 6-azauracil (which slows elongation) suppresses the ssu72-2 growth defect, indicating Ssu72 negatively influences RNAP II during transcription. Biochemical fractionation, co-immunoprecipitation, genetic interaction (6-AU suppression), transcription assays Molecular cell High 12453421
2003 Ssu72 is required for 3' end cleavage of pre-mRNA but is dispensable for poly(A) addition and RNAP II termination; Ssu72 interacts physically with the Pta1 subunit of CPF, and physical interactions of Ssu72 and Sub1 with Pta1 are mutually exclusive. Biochemical depletion/rescue in vitro cleavage assay, co-immunoprecipitation, genetic overexpression/lethality assays Genes & development High 12704082
2003 Ssu72 is a phosphatase structurally related to low-molecular-weight protein tyrosine phosphatases (LMWPTPs); recombinant Ssu72 cleaves p-nitrophenylphosphate and is inhibited by PTPase inhibitors; the catalytic cysteine in the CX5R motif is essential for activity in vitro and for viability in vivo. In vitro phosphatase activity assay (pNPP substrate), PTPase inhibitor treatment, active-site mutagenesis, in vivo complementation The Journal of biological chemistry High 12606538
2003 Ssu72 is essential for transcription termination of snoRNAs and specific mRNAs in yeast; ssu72-ts69 mutant shows read-through transcription of snoRNAs and some mRNAs; Ssu72 physically interacts with the CTD kinase Kin28 and functionally interacts with the CTD phosphatase Fcp1. Genome-wide expression analysis, northern blotting, co-immunoprecipitation, genetic interaction The EMBO journal High 12660165
2003 ssu72 mutations disrupt both Nrd1-dependent (poly(A)-independent, snoRNA) termination and poly(A)-dependent termination, demonstrating that Ssu72 mediates both termination pathways and that they share a common mechanism. Genetic selection, reporter assays for termination, in vivo transcription readthrough analysis Molecular and cellular biology High 12944462
2004 Ssu72, a component of yeast CPF, is an RNA polymerase II CTD phosphatase with specificity for Ser5-P (not Ser2-P); it catalyzes CTD Ser5-P dephosphorylation in association with the Pta1 subunit of CPF; depletion of Ssu72 impairs transcription in vitro and this defect is rescued by catalytically active recombinant Ssu72; the essential role in 3' end processing is independent of catalytic activity. In vitro CTD phosphatase assay, depletion/rescue with recombinant protein, in vitro transcription, active-site mutagenesis Molecular cell High 15125841
2005 Human Ssu72 (hSsu72) interacts with pRb (identified in yeast two-hybrid screen), associates with TFIIB and yeast Pta1, exhibits intrinsic phosphatase activity, and localizes primarily to the cytoplasm in mammalian cells; fusion to a strong NLS conferred nuclear localization only in a fraction of cells, suggesting active cytoplasmic tethering. Yeast two-hybrid, co-immunoprecipitation in transfected mammalian cells, subcellular fractionation/imaging, in vitro phosphatase assay, siRNA knockdown Nucleic acids research Medium 15659578
2006 Ssu72-R129A (ssu72-2) is catalytically impaired in vitro and causes accumulation of Ser5-P RNAP II in vivo; an in vitro transcription system from ssu72-2 shows impaired elongation efficiency; suppressors in RPB1 (R1281A) and RPB2 (R983G, rpb2-4, rpb2-10, encoding slow forms of RNAP II) and deletion of SPT4 suppress ssu72-2, placing Ssu72 as a transcription elongation factor that facilitates the RNAP II transition into elongation by dephosphorylating Ser5-P after capping. In vitro phosphatase assay, in vivo CTD phosphorylation (western blot), in vitro transcription elongation assay, genetic suppressor screen Molecular and cellular biology High 17101794
2009 The N-terminal region of Pta1 (first 75 aa) is required for snoRNA termination, CTD Ser5-P dephosphorylation, and gene looping but not for mRNA 3' end processing; different Pta1 regions interact with CPF subunits Ssu72, Pti1, and Ysh1; the first 300 aa of Pta1 suffice for interaction with Ssu72; loss of Pta1 leads to loss of Ssu72 protein. Deletion mutagenesis, degron-mediated depletion, co-immunoprecipitation, in vitro processing assays, 3C gene looping assay Molecular and cellular biology High 19188448
2010 Crystal structure of human symplekin N-terminal domain (ARM/HEAT fold) in ternary complex with human Ssu72 and a CTD Ser5 phosphopeptide at 2.4 Å: Ssu72 binds the concave face of symplekin; the pSer5-Pro6 peptide bond is in cis configuration in the active site (unique among CTD peptide conformations); symplekin N-terminal domain stimulates Ssu72 CTD phosphatase activity in vitro; engineered mutations at the symplekin-Ssu72 interface abolish interaction; symplekin N-terminal domain inhibits polyadenylation in vitro when coupled to transcription, and catalytically active Ssu72 overcomes this inhibition. X-ray crystallography (2.4 Å), in vitro phosphatase activity assay, in vitro polyadenylation coupled to transcription, interface mutagenesis Nature High 20861839
2010 Crystal structure of Ssu72 in complex with a CTD Ser5-P substrate reveals that the cis-Ser5-P-Pro6 isomer (minor in solution) is the preferred substrate; Ess1 (Pin1)-catalyzed cis-trans proline isomerization facilitates rapid dephosphorylation by Ssu72, providing the first structural evidence of a cis-proline-specific enzyme; this is required for CTD-mediated snRNA termination. X-ray crystallography, NMR, in vitro phosphatase kinetics, Ess1/Pin1 isomerization assays The Journal of biological chemistry High 21159777
2011 Crystal structures of Drosophila Ssu72 apo and in complex with vanadate (transition-state analogue) at 2.35 Å reveal a covalent phosphoryl-enzyme intermediate with the catalytic cysteine; Ssu72 has a core LMWPTP fold with a unique 'cap' domain sheltering the active site; mutagenesis of five residues (Met17, Pro46, Asp51, Tyr77, Met85) in the substrate-binding groove established their essential roles in substrate recognition. X-ray crystallography (apo and vanadate complex), active-site mutagenesis, differential scanning fluorimetry The Biochemical journal High 21204787
2012 Ssu72 is responsible for erasing phospho-Ser7 (Ser7-P) marks on the RNAP II CTD; Ser7E phospho-mimic substitution is lethal; removal of CTD phospho-marks during transcription termination is mechanistically coupled; inability to remove these marks prevents efficient Pol II termination and likely impedes PIC assembly. In vivo lethality assay (phospho-mimic), CTD phospho-mass spectrometry, ChIP, in vitro phosphatase assay, genetic analysis The Journal of biological chemistry High 22235117
2012 Crystal structure of human symplekin N-terminal domain / human Ssu72 / pSer7 CTD peptide ternary complex reveals the pSer7 peptide binds in the Ssu72 active site with its backbone running in the opposite direction compared to the pSer5 peptide; pSer7 phosphatase activity of Ssu72 is ~4000-fold lower than pSer5 activity toward peptide substrate. X-ray crystallography, in vitro CTD phosphatase kinetics Genes & development High 23070812
2013 Aurora B kinase directly interacts with and phosphorylates Ssu72 at Ser19 in vitro and in vivo; Aurora B-mediated phosphorylation of Ssu72 causes structural modification, downregulates Ssu72 phosphatase activity, and triggers ubiquitin-dependent degradation of Ssu72; overexpression of the Aurora B phosphomimetic Ssu72 mutant prevents maintenance of chromosome arm cohesion, placing Ssu72 as a cohesin-binding phosphatase regulated by Aurora B during early mitosis. In vitro kinase assay, in vitro phosphatase assay, co-immunoprecipitation, ubiquitination assay, overexpression of phosphomimetic mutant, chromosome cohesion assay Nature communications High 24149858
2013 Phosphorylated Thr4 adjacent to Ser5 in the CTD reduces Ssu72 phosphatase activity toward Ser5-P by 4-fold but does not abolish it; Ssu72 does not dephosphorylate Thr4; crystal structure of Drosophila Ssu72-symplekin with doubly phosphorylated Thr4/Ser5 CTD peptide shows the CTD adopts almost identical conformation to the Ser5-P alone substrate. X-ray crystallography, mass spectrometry, in vitro phosphatase kinetics ACS chemical biology High 23844594
2014 Ssu72 dephosphorylates Ser5-P at the initiation-elongation transition in vivo (ChIP analysis); Ssu72 also indirectly affects Ser2-P levels during elongation, but this effect is independent of its catalytic activity; Ssu72 interacts with initiation machinery components yet is integral to CPF, providing a dual role at initiation-elongation transition. ChIP analysis of CTD phosphorylation states, in vitro phosphatase assay, catalytic mutant analysis The Journal of biological chemistry High 25339178
2014 HIV-1 Tat directly interacts with Ssu72 and strongly stimulates its CTD Ser5-P phosphatase activity; Ssu72 is essential for Tat:P-TEFb-mediated phosphorylation of the Ser5-P CTD in vitro; Ssu72 is recruited by Tat to the HIV-1 proviral promoter (ChIP); Ssu72 predominantly colocalizes with Ser5-P RNAP II at promoters in human embryonic stem cells (ChIP-seq). Direct binding assay, in vitro CTD phosphatase assay, ChIP, ChIP-seq, GRO-seq, siRNA knockdown Genes & development High 25319827
2015 Liver-specific conditional knockout of Ssu72 in mice causes impaired hepatocyte polyploidization, aberrant cell cycle progression (G2/M arrest), DNA endoreplication, and increased markers of liver injury; Ssu72 regulates the restriction point of the cell cycle in hepatocytes. Conditional knockout mouse model, flow cytometry, histology, liver injury markers Hepatology Medium 26458163
2017 Ssu72 overexpression suppresses STAT3 activation and Th17 cell differentiation in vitro; systemic Ssu72 infusion attenuates experimental autoimmune arthritis by reducing p-STAT3 levels and Th17 cell formation in vivo. In vitro T cell differentiation assay, in vivo arthritis model, phospho-STAT3 western blot, systemic protein infusion Scientific reports Medium 28710354
2019 Ssu72 phosphatase controls telomere replication termination in fission yeast by regulating Stn1 phosphorylation at Ser74 (within its OB-fold domain), controlling Stn1 recruitment to telomeres; ssu72Δ mutants show long 3'-ssDNA overhangs indicating defective lagging-strand DNA synthesis; human SSU72 similarly regulates hSTN1 recruitment to telomeres and telomerase activation. Fission yeast genetics (ssu72Δ), telomere ChIP, telomere southern blot, in vitro phosphatase assay, human cell siRNA knockdown The EMBO journal High 30796050
2019 Human Ssu72 is physically associated with early RNA polymerase II elongation complexes and enters the transcription cycle during PIC formation; Ssu72 activity on elongation complexes is strictly limited to complexes containing RNA ≤28 nt; additional factor(s) present in PICs regulate this cutoff. In vitro transcription elongation complex reconstitution, CTD phosphatase assay on isolated elongation complexes, salt-wash stability assay PloS one Medium 30901332
2020 Fission yeast Pin1 (peptidyl-prolyl isomerase) directly recruits Ssu72 phosphatase to the CTD to facilitate dephosphorylation during oxidative stress-responsive transcription; Pin1 promotes dissociation of Sty1 MAPK from the CTD, and Ssu72 then dephosphorylates CTD for elongation; this mechanism is conserved in human cells. Co-immunoprecipitation, genetic analysis (pin1Δ), ChIP, transcription reporter assays, conservation analysis in human cells Nucleic acids research Medium 33410907
2020 In fission yeast, Pin1 (prolyl isomerase) acts as a positive effector of 3' processing/termination via Ssu72; transcriptional profiling shows ~77% of genes downregulated in pin1Δ are also downregulated when Ssu72 is inactivated, placing Pin1 upstream of Ssu72 in CTD-mediated 3' processing/termination. Genetic epistasis, transcriptional profiling, conditional inactivation of Ssu72 Nucleic acids research Medium 32282918
2020 Ssu72 directly binds to the GM-CSF receptor β-chain in alveolar macrophages (following GM-CSF stimulation) and prevents its phosphorylation; Ssu72-deficient AMs show higher phosphorylation of GM-CSFR β-chain and downstream molecules, causing dysregulation of cell cycle, cell death, and mitochondrial metabolism; JAK2 inhibitor rescues the phenotype. Conditional knockout mouse (LysM-Cre, Cd11c-Cre), co-immunoprecipitation, phospho-western blot, adoptive transfer, JAK2 inhibitor rescue The Journal of allergy and clinical immunology Medium 32910932
2021 Ssu72 is activated by TCR and IL-2R signaling pathways and localizes to the cell membrane; Ssu72 forms a complex with PLCγ1 (essential TCR signaling effector); Ssu72 deficiency in T cells disrupts CD4+ T cell differentiation into Tregs, impairs PLCγ1 downstream signaling, and fails to induce Foxp3. Conditional T cell KO (Cd4-Cre), co-immunoprecipitation, flow cytometry, cytokine measurement, subcellular localization imaging Cellular & molecular immunology Medium 33850312
2021 Ssu72 acts as a tyrosine phosphatase for ZAP-70 in T cells; affinity purification-mass spectrometry and in vitro assay demonstrated specific Ssu72-ZAP-70 interaction; recombinant Ssu72 reduces tyrosine phosphorylation of ZAP-70 in vitro via its phosphatase activity; Ssu72-deficient T cells show hyperphosphorylation of ZAP-70 and downstream TCR signaling molecules. Affinity purification-mass spectrometry, in vitro phosphatase assay with recombinant proteins, conditional KO (Cd4-Cre), phospho-western blot, flow cytometry Proceedings of the National Academy of Sciences of the United States of America High 34452999
2021 Hepatic Ssu72 loss results in hypo-phosphorylation of HNF4α (a master regulator of hepatocyte function) and orchestrates dedifferentiation of mature hepatocytes to progenitor cells; Ssu72-mediated HNF4α transcription contributes to steatohepatitis-associated HCC progression. Liver-specific conditional KO mouse, phospho-western blot, hepatocyte dedifferentiation assay, chemical and metabolic HCC models Cell death and differentiation Medium 34616001
2022 Avian influenza virus NS1 protein directly binds to SSU72 and causes its degradation, inducing transcriptional readthrough (TRT) at downstream 'trans' genes; TRT suppresses STAT1/2 expression and impairs innate immune responses; SSU72 overexpression reduces TRT and alleviates lung injury. Co-immunoprecipitation (NS1-SSU72), protein degradation assay, transcriptional readthrough analysis, mouse model, patient PBMCs, siRNA/overexpression Cellular & molecular immunology Medium 35332300
2023 Ssu72 phosphatase is essential for thermogenesis in brown adipose tissue; Ssu72 dephosphorylates eIF2α, and Ssu72 deficiency leads to hyperphosphorylation of eIF2α, altering cytosolic mRNA translation of mitochondrial OXPHOS subunits, resulting in mitochondrial dysfunction and defective thermogenesis; cold exposure increases Ssu72 expression in BAT. Adipocyte-specific conditional KO mouse, cold tolerance test, polysome profiling, phospho-western blot (eIF2α), mitochondrial function assays, rescue by Ssu72 re-expression Nature communications High 36841836

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Ssu72 Is an RNA polymerase II CTD phosphatase. Molecular cell 192 15125841
2010 Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex. Nature 144 20861839
2002 A role for SSU72 in balancing RNA polymerase II transcription elongation and termination. Molecular cell 141 12453421
2003 Functional interactions between the transcription and mRNA 3' end processing machineries mediated by Ssu72 and Sub1. Genes & development 125 12704082
2010 cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. The Journal of biological chemistry 109 21159777
2003 Ssu72 is a phosphatase essential for transcription termination of snoRNAs and specific mRNAs in yeast. The EMBO journal 106 12660165
2003 Ssu72 protein mediates both poly(A)-coupled and poly(A)-independent termination of RNA polymerase II transcription. Molecular and cellular biology 102 12944462
2012 Ssu72 phosphatase-dependent erasure of phospho-Ser7 marks on the RNA polymerase II C-terminal domain is essential for viability and transcription termination. The Journal of biological chemistry 85 22235117
1996 Synthetic enhancement of a TFIIB defect by a mutation in SSU72, an essential yeast gene encoding a novel protein that affects transcription start site selection in vivo. Molecular and cellular biology 85 8657130
1999 Mutational analysis of yeast TFIIB. A functional relationship between Ssu72 and Sub1/Tsp1 defined by allele-specific interactions with TFIIB. Genetics 75 10511545
2000 Functional interaction between Ssu72 and the Rpb2 subunit of RNA polymerase II in Saccharomyces cerevisiae. Molecular and cellular biology 53 11046131
2009 The essential N terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3'-end processing. Molecular and cellular biology 50 19188448
2003 The mRNA transcription/processing factor Ssu72 is a potential tyrosine phosphatase. The Journal of biological chemistry 46 12606538
2006 Role for the Ssu72 C-terminal domain phosphatase in RNA polymerase II transcription elongation. Molecular and cellular biology 45 17101794
2012 An unexpected binding mode for a Pol II CTD peptide phosphorylated at Ser7 in the active site of the CTD phosphatase Ssu72. Genes & development 40 23070812
2011 Crystal structure of Ssu72, an essential eukaryotic phosphatase specific for the C-terminal domain of RNA polymerase II, in complex with a transition state analogue. The Biochemical journal 31 21204787
2013 novel modifications on C-terminal domain of RNA polymerase II can fine-tune the phosphatase activity of Ssu72. ACS chemical biology 28 23844594
2005 Conserved and specific functions of mammalian ssu72. Nucleic acids research 27 15659578
2015 Hepatocyte homeostasis for chromosome ploidization and liver function is regulated by Ssu72 protein phosphatase. Hepatology (Baltimore, Md.) 24 26458163
2014 The Ssu72 phosphatase mediates the RNA polymerase II initiation-elongation transition. The Journal of biological chemistry 24 25339178
2014 A gene-specific role for the Ssu72 RNAPII CTD phosphatase in HIV-1 Tat transactivation. Genes & development 20 25319827
2013 Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion. Nature communications 20 24149858
2017 Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation. Scientific reports 18 28710354
2014 Vertebrate Ssu72 regulates and coordinates 3'-end formation of RNAs transcribed by RNA polymerase II. PloS one 17 25166011
2020 Genetic interactions and transcriptomics implicate fission yeast CTD prolyl isomerase Pin1 as an agent of RNA 3' processing and transcription termination that functions via its effects on CTD phosphatase Ssu72. Nucleic acids research 16 32282918
2020 Ssu72 regulates alveolar macrophage development and allergic airway inflammation by fine-tuning of GM-CSF receptor signaling. The Journal of allergy and clinical immunology 13 32910932
2019 Ssu72 phosphatase is a conserved telomere replication terminator. The EMBO journal 12 30796050
2023 Ssu72 phosphatase is essential for thermogenic adaptation by regulating cytosolic translation. Nature communications 9 36841836
2022 Avian influenza viruses suppress innate immunity by inducing trans-transcriptional readthrough via SSU72. Cellular & molecular immunology 9 35332300
2021 Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells. Cellular & molecular immunology 9 33850312
2019 Functional interaction of human Ssu72 with RNA polymerase II complexes. PloS one 9 30901332
2005 Kinase Cak1 functionally interacts with the PAF1 complex and phosphatase Ssu72 via kinases Ctk1 and Bur1. Molecular genetics and genomics : MGG 9 16362371
2021 Ssu72 Dual-Specific Protein Phosphatase: From Gene to Diseases. International journal of molecular sciences 8 33917542
2021 Ssu72-HNF4α signaling axis classify the transition from steatohepatitis to hepatocellular carcinoma. Cell death and differentiation 8 34616001
2020 Ssu72 Regulates Fungal Development, Aflatoxin Biosynthesis and Pathogenicity in Aspergillus flavus. Toxins 7 33202955
2020 Diverse and conserved roles of the protein Ssu72 in eukaryotes: from yeast to higher organisms. Current genetics 7 33244642
2021 Ssu72 phosphatase directly binds to ZAP-70, thereby providing fine-tuning of TCR signaling and preventing spontaneous inflammation. Proceedings of the National Academy of Sciences of the United States of America 6 34452999
2021 The fission yeast Pin1 peptidyl-prolyl isomerase promotes dissociation of Sty1 MAPK from RNA polymerase II and recruits Ssu72 phosphatase to facilitate oxidative stress induced transcription. Nucleic acids research 5 33410907
2013 Structurally conserved and functionally divergent yeast Ssu72 phosphatases. FEBS letters 5 23831060
2023 Phosphatase Ssu72 Is Essential for Homeostatic Balance Between CD4+ T Cell Lineages. Immune network 2 37179750
2011 ¹H, ¹³C and ¹⁵N backbone and side-chain resonance assignments of Drosophila melanogaster Ssu72. Biomolecular NMR assignments 2 21732054
2024 Ssu72: a versatile protein with functions in transcription and beyond. Frontiers in molecular biosciences 1 38304578
2024 Ssu72 phosphatase deficiency leads to spindle crossing during the second meiotic division process. Yi chuan = Hereditas 0 38886153
2024 Deciphering significant interaction between Clp1 (CF IA) and Ssu72 (CPF) in pre-mRNA processing via in silico approaches. Journal of biomolecular structure & dynamics 0 39522172