Affinage

SCYL1

N-terminal kinase-like protein · UniProt Q96KG9

Round 2 corrected
Length
808 aa
Mass
89.6 kDa
Annotated
2026-04-28
130 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCYL1 is a catalytically inactive pseudokinase that functions as a scaffolding adaptor in COPI-mediated retrograde membrane trafficking and in nuclear tRNA export. It oligomerizes via central HEAT repeats and uses a C-terminal RKXX-COO⁻ motif to bind the γ2-COP appendage domain, selectively linking class II Arfs (Arf4) to γ2-COP-containing COPI subcomplexes at the ERGIC and cis-Golgi; its loss disrupts COPI-dependent KDEL receptor recycling and causes Golgi disorganization (PMID:18556652, PMID:24481816, PMID:20209057). SCYL1 also participates in nuclear tRNA export by forming a quaternary complex with exportin-t, tRNA, and RanGTP at the nuclear pore (PMID:20505071). Neural-specific loss of Scyl1 in mice causes progressive lower motor neuron degeneration with cytoplasmic TDP-43 and ubiquilin 2 accumulation, cerebellar Purkinje cell loss, and optic nerve atrophy, establishing a cell-autonomous neuronal requirement (PMID:17571074, PMID:23175812).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2007 High

    Positional cloning of the murine mdf locus identified Scyl1 as a neuronally-expressed pseudokinase whose loss causes cerebellar atrophy and Purkinje cell degeneration, establishing it as essential for neuronal survival but leaving its molecular function unknown.

    Evidence Positional cloning and loss-of-function mutation mapping in mdf mice with immunohistochemistry

    PMID:17571074

    Open questions at the time
    • Molecular mechanism by which SCYL1 supports neuronal viability was unknown
    • Whether SCYL1 functions cell-autonomously in neurons was untested
    • No binding partners or pathway placement identified
  2. 2008 High

    Discovery that SCYL1 directly binds COPI coat components via a C-terminal RKLD-COO⁻ motif and is required for retrograde KDEL receptor trafficking placed this pseudokinase in the COPI-dependent ER-Golgi recycling pathway.

    Evidence Mass spectrometry screen, co-IP from brain lysates, siRNA knockdown with KDEL receptor trafficking assay

    PMID:18556652

    Open questions at the time
    • Which specific COPI subunit(s) SCYL1 engages was not resolved
    • Whether SCYL1 links COPI to specific Arf GTPases was unknown
    • Connection between COPI trafficking role and neurodegeneration not established
  3. 2010 Medium

    Two parallel studies expanded SCYL1's functional repertoire: one showed SCYL1 depletion disrupts Golgi architecture and placed it at the golgin p115/58K network interface, while another demonstrated SCYL1 forms a quaternary complex with exportin-t, tRNA, and RanGTP, implicating it in nuclear tRNA export.

    Evidence siRNA knockdown with 3D confocal and EM for Golgi morphology; in vitro reconstitution of exportin-t/tRNA/SCYL1/RanGTP complex and tRNA export rescue in COS-7 cells

    PMID:20209057 PMID:20505071

    Open questions at the time
    • Relative physiological importance of tRNA export versus COPI trafficking roles not resolved
    • Whether tRNA export function is relevant to the neurodegenerative phenotype is unknown
    • Golgi morphology study from a single lab without independent replication
  4. 2012 High

    Neural-specific conditional knockout demonstrated SCYL1 acts cell-autonomously in neurons, and linked its loss to cytoplasmic TDP-43 and ubiquilin 2 accumulation in lower motor neurons — hallmarks of ALS pathology — bridging the trafficking role to a neurodegeneration-relevant mechanism.

    Evidence Conditional neural-specific and muscle-specific Scyl1 knockout mice with TDP-43 and ubiquilin 2 immunolocalization

    PMID:23175812

    Open questions at the time
    • Causal chain from COPI trafficking defect to TDP-43 mislocalization not delineated
    • Whether SCYL1 loss causes TDP-43 aggregation through impaired autophagy, proteasome dysfunction, or another route is unresolved
    • No human genetic disease association demonstrated
  5. 2014 High

    Biochemical mapping revealed SCYL1 oligomerizes through HEAT repeats and acts as a selective scaffold linking class II Arfs (Arf4) to γ2-COP-containing COPI subcomplexes via distinct binding sites, providing a structural explanation for its specificity in retrograde trafficking.

    Evidence Pull-down assays mapping γ2-COP appendage domain interaction; Arf4-selective binding; dominant-negative and knockdown with Golgi morphology readout

    PMID:24481816

    Open questions at the time
    • No high-resolution structural model of the SCYL1–γ2-COP–Arf4 ternary complex
    • Whether additional cargo adaptors cooperate with SCYL1 at the ERGIC is unknown
    • Functional significance of SCYL1 pseudokinase domain remains uncharacterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanistic link between SCYL1's COPI scaffolding and/or tRNA export roles and the downstream TDP-43 mislocalization causing motor neuron degeneration remains unresolved, as does the functional significance of the catalytically inactive kinase-like domain.
  • No causal pathway connecting COPI trafficking or tRNA export defects to TDP-43 proteinopathy
  • Pseudokinase domain function or potential non-canonical catalytic activity not addressed
  • Human genetic validation as a Mendelian disease gene for neurodegeneration not reported in this timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1
Localization
GO:0005794 Golgi apparatus 3 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ARF4COPG2FTCDNUP98RANXPOT
Complex memberships
COPI coat complex (accessory/scaffold)exportin-t/RanGTP tRNA export complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Loss-of-function mutation in Scyl1, encoding an evolutionarily conserved N-terminal kinase-like (pseudokinase) protein, was identified as the cause of the autosomal recessive murine neurodegenerative disease 'muscle deficient' (mdf), characterized by cerebellar atrophy, Purkinje cell loss, and optic nerve atrophy. Scyl1 was found to be prominently expressed in neurons and enriched at CNS synapses and neuromuscular junctions. Positional cloning and loss-of-function mutation mapping in mdf mice; immunohistochemistry and expression analysis EMBO reports High 17571074
2008 SCYL1 (Scy1-like 1) was identified as a binding partner of COPI coat components (coatomer). SCYL1 uses a C-terminal RKLD-COO⁻ sequence (analogous to the KKXX-COO⁻ motif of transmembrane ER-resident proteins) to bind COPI coats. SCYL1 co-localizes with βCOP at the ER-Golgi intermediate compartment (ERGIC) and cis-Golgi in an Arf1-independent manner, and siRNA-mediated knockdown of SCYL1 disrupts COPI-mediated retrograde trafficking of the KDEL receptor to the ER without affecting anterograde traffic. Mass spectrometry-based binding partner screen, pull-down assays, co-immunoprecipitation from brain lysates, siRNA knockdown with KDEL receptor trafficking assay, immunofluorescence co-localization The Journal of biological chemistry High 18556652
2010 SCYL1 knockdown causes an increase in Golgi surface area and volume and disorganization of Golgi ultrastructure (increased cisternal luminal width), without disrupting Golgi polarity or cisternal number. SCYL1 localizes to the Golgi in a manner dependent on the golgin p115 network, and SCYL1 interacts with the cis-Golgi-associated protein 58K/FTCD (formiminotransferase cyclodeaminase), placing SCYL1 at the interface of the golgin network and COPI trafficking. siRNA knockdown with 3D confocal imaging and electron microscopy of Golgi morphology; co-immunoprecipitation of SCYL1 with 58K/FTCD; immunofluorescence after p115 knockdown PloS one Medium 20209057
2010 SCYL1 functions as a cytoplasmic component of the mammalian nuclear tRNA export machinery. SCYL1 binds tRNA saturably, associates with the nuclear pore complex via interaction with Nup98, and co-purifies with exportin-t, exportin-5, RanGTPase, and eEF-1A. SCYL1 interacts directly with exportin-t and RanGTP (but not RanGDP) in vitro, and exportin-t/tRNA/SCYL1/RanGTP form a quaternary complex in vitro. Overexpression of SCYL1 rescues export of a nuclear export-defective tRNA mutant in COS-7 cells. In vitro tRNA binding assay, co-purification/co-immunoprecipitation with nuclear pore and export machinery components, in vitro reconstitution of quaternary complex, functional rescue assay in COS-7 cells Molecular biology of the cell Medium 20505071
2012 Neural-specific deletion of Scyl1 is sufficient to cause progressive lower motor neuron (LMN) degeneration and motor dysfunction in mice, demonstrating that SCYL1 acts in a cell-autonomous manner in neurons. Loss of Scyl1 results in mislocalization and accumulation of TDP-43 and ubiquilin 2 into cytoplasmic inclusions within LMNs—a pathological hallmark of ALS. Skeletal muscle-specific deletion does not cause motor dysfunction, confirming the neural cell-autonomous requirement. Conditional (neural-specific and muscle-specific) Scyl1 knockout mice; immunofluorescence and immunohistochemistry for TDP-43 and ubiquilin 2 localization; neuropathological analysis of motor neurons and peripheral nerves The Journal of neuroscience High 23175812
2014 SCYL1 oligomerizes through centrally located HEAT repeats and uses its C-terminal RKXX-COO⁻ motif to interact directly with the appendage domain of coatomer subunit γ-2 (γ2-COP/COPG2). Through a distinct binding site, SCYL1 selectively interacts with class II Arfs (notably Arf4), thereby functioning as a scaffold that links class II Arfs specifically to γ2-COP-containing COPI subcomplexes. Disruption of this scaffolding causes tubulation of the ERGIC and cis-Golgi, similar to loss of Arf or Arf-GEF function. Pull-down assays mapping direct interaction with γ2-COP appendage domain; identification of Arf4-selective binding; dominant-negative and knockdown approaches with Golgi morphology readout (confocal and electron microscopy) Journal of cell science High 24481816

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature genetics 958 22504420
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2019 Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Molecular cell 296 31006538
1991 Generation of p50 subunit of NF-kappa B by processing of p105 through an ATP-dependent pathway. Nature 294 1956402
1992 A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. Molecular and cellular biology 283 1531086
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
1990 Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. Journal of virology 254 2159546
1992 The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding. Proceedings of the National Academy of Sciences of the United States of America 238 1532257
2000 Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. Genome research 226 11042159
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
1995 Human cytomegalovirus upregulates NF-kappa B activity by transactivating the NF-kappa B p105/p50 and p65 promoters. Journal of virology 221 7636984
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2012 Functional genomics identifies therapeutic targets for MYC-driven cancer. Proceedings of the National Academy of Sciences of the United States of America 203 22623531
2006 Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS biology 203 16903783
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
1993 Proteolytic degradation of MAD3 (I kappa B alpha) and enhanced processing of the NF-kappa B precursor p105 are obligatory steps in the activation of NF-kappa B. Nucleic acids research 187 8255759
1999 TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105. Nature 184 9950430
1997 The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas. Nature medicine 179 9256285
1992 The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50. The EMBO journal 178 1639070
1999 NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of Bcl-3-p50 complexes. The EMBO journal 174 10469655
2010 A genome-wide association study of optic disc parameters. PLoS genetics 170 20548946
1996 A glycine-rich region in NF-kappaB p105 functions as a processing signal for the generation of the p50 subunit. Molecular and cellular biology 166 8628291
2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling 162 25468996
2009 Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95-p105. Science signaling 161 19531803
2000 SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase. The EMBO journal 156 10835356
1992 Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105. Oncogene 150 1501885
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
1993 The NF-kappa B precursor p105 and the proto-oncogene product Bcl-3 are I kappa B molecules and control nuclear translocation of NF-kappa B. The EMBO journal 148 8428580
2003 Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability. The Journal of biological chemistry 139 12871932
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2006 Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. The Journal of clinical investigation 133 17124531
1997 Induction of the transcription factor Sp1 during human cytomegalovirus infection mediates upregulation of the p65 and p105/p50 NF-kappaB promoters. Journal of virology 133 9151857
2009 The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Molecular cell 130 19524538
1996 Effects on NF-kappa B1/p105 processing of the interaction between the HTLV-1 transactivator Tax and the proteasome. Nature 129 8692272
1991 Functional analysis of E2-mediated repression of the HPV18 P105 promoter. The New biologist 129 1645591
1998 Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p)105 precursor (NF-kappaB1) but expressing p50. The Journal of experimental medicine 117 9529315
2003 betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932. Molecular and cellular biology 116 12482991
2001 Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis. The Journal of biological chemistry 112 11297557
2003 NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity. Molecular and cellular biology 107 12832462
1992 Molecular cloning and characterization of a novel Rel/NF-kappa B family member displaying structural and functional homology to NF-kappa B p50/p105. DNA and cell biology 103 1388725
2013 Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol-resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation. International journal of nanomedicine 97 23319859
1999 Structural motifs involved in ubiquitin-mediated processing of the NF-kappaB precursor p105: roles of the glycine-rich region and a downstream ubiquitination domain. Molecular and cellular biology 97 10207090
1997 Regulation of NFKB1 proteins by the candidate oncoprotein BCL-3: generation of NF-kappaB homodimers from the cytoplasmic pool of p50-p105 and nuclear translocation. The EMBO journal 97 9218802
1993 Promoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL. Journal of immunology (Baltimore, Md. : 1950) 97 8454856
2015 KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth. Cell 93 25860612
1993 Common structural constituents confer I kappa B activity to NF-kappa B p105 and I kappa B/MAD-3. The EMBO journal 91 8334994
2000 Cotranslational dimerization of the Rel homology domain of NF-kappaB1 generates p50-p105 heterodimers and is required for effective p50 production. The EMBO journal 90 10970863
1994 Tax induces nuclear translocation of NF-kappa B through dissociation of cytoplasmic complexes containing p105 or p100 but does not induce degradation of I kappa B alpha/MAD3. Journal of virology 83 7966593
1987 Modulation of the nuclear antigen p105 as a function of cell-cycle progression. Journal of cellular physiology 82 3549742
2008 Scyl1, mutated in a recessive form of spinocerebellar neurodegeneration, regulates COPI-mediated retrograde traffic. The Journal of biological chemistry 78 18556652
1998 NF-kappa B p105 processing via the ubiquitin-proteasome pathway. The Journal of biological chemistry 77 9430676
2004 Myocardial protection by remote preconditioning: the role of nuclear factor kappa-B p105 and inducible nitric oxide synthase. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 72 15519191
1996 Phosphorylation of p105 PEST sequence via a redox-insensitive pathway up-regulates processing of p50 NF-kappaB. The Journal of biological chemistry 70 8626394
1992 p105, the NF-kappa B p50 precursor protein, is one of the cellular proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells. Journal of virology 70 1533881
2010 miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. Cancer research 68 20713524
1997 Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors, but not with the processing of p105/NF-kappa B1 in T cells. European journal of immunology 68 9247567
2002 The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105. The Journal of biological chemistry 67 11953428
1993 HTLV-I encoded Tax in association with NF-kappa B precursor p105 enhances nuclear localization of NF-kappa B p50 and p65 in transfected cells. Oncogene 64 8414497
2008 Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation. Nature immunology 60 19060899
1998 Enzymes catalyzing ubiquitination and proteolytic processing of the p105 precursor of nuclear factor kappaB1. The Journal of biological chemistry 60 9535861
2007 Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration. EMBO reports 59 17571074
2005 Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide. Proceedings of the National Academy of Sciences of the United States of America 56 15699325
2012 Coordinate regulation of TPL-2 and NF-κB signaling in macrophages by NF-κB1 p105. Molecular and cellular biology 55 22733995
1995 Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus. Journal of virology 53 7853483
2004 Dual effects of IkappaB kinase beta-mediated phosphorylation on p105 Fate: SCF(beta-TrCP)-dependent degradation and SCF(beta-TrCP)-independent processing. Molecular and cellular biology 52 14673179
2001 Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105. Biochimie 52 11295495
2010 Scyl1 regulates Golgi morphology. PloS one 50 20209057
2005 BCL-6 negatively regulates expression of the NF-kappaB1 p105/p50 subunit. Journal of immunology (Baltimore, Md. : 1950) 49 15611242
2000 17 beta-estradiol inhibits tumor necrosis factor-alpha-induced nuclear factor-kappa B activation by increasing nuclear factor-kappa B p105 level in MCF-7 breast cancer cells. Biochemical and biophysical research communications 49 11112416
1990 Binding of p53 and p105-RB is not sufficient for oncogenic transformation by a hybrid polyomavirus-simian virus 40 large T antigen. Journal of virology 49 2214017
2005 High levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins. Virology 47 15629778
1998 Ceramide activates NFkappaB by inducing the processing of p105. The Journal of biological chemistry 46 9624136
1992 Identification of complex formation between two intracellular tyrosine kinase substrates: human c-Rel and the p105 precursor of p50 NF-kappa B. Oncogene 46 1437141
1990 Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics. The American journal of pathology 45 1979714
2012 Omega-3 docosahexaenoic acid and procyanidins inhibit cyclo-oxygenase activity and attenuate NF-κB activation through a p105/p50 regulatory mechanism in macrophage inflammation. The Biochemical journal 44 21954853
1995 Downregulation of MHC class I expression due to interference with p105-NF kappa B1 processing by Ad12E1A. The EMBO journal 44 7729425
1992 Chromosomal localization of the genes encoding the p50/p105 subunits of NF-kappa B (NFKB2) and the I kappa B/MAD-3 (NFKBI) inhibitor of NF-kappa B to 4q24 and 14q13, respectively. Genomics 44 1427874
2016 Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/d-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment. International journal of nanomedicine 42 27932881
2009 NF-kappa B1 p105 regulates T cell homeostasis and prevents chronic inflammation. Journal of immunology (Baltimore, Md. : 1950) 42 19234210
1988 Flow cytometric analysis of pituitary tumors. Correlation of nuclear antigen p105 and DNA content with clinical behavior. Cancer 42 3048631
1994 Alternative splicing of RNA transcripts encoded by the murine p105 NF-kappa B gene generates I kappa B gamma isoforms with different inhibitory activities. Proceedings of the National Academy of Sciences of the United States of America 41 8183915
2014 Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating. Journal of drug targeting 39 24806516
2013 O-GlcNAcylation and p50/p105 binding of c-Rel are dynamically regulated by LPS and glucosamine in BV2 microglia cells. British journal of pharmacology 39 23646894
2014 Scyl1 scaffolds class II Arfs to specific subcomplexes of coatomer through the γ-COP appendage domain. Journal of cell science 38 24481816
1993 Skin-specific expression of a truncated E1a oncoprotein binding to p105-Rb leads to abnormal hair follicle maturation without increased epidermal proliferation. The Journal of cell biology 38 7684738
2009 NF-kappaB signalling proteins p50/p105, p52/p100, RelA, and IKKepsilon are over-expressed in oesophageal squamous cell carcinomas. Pathology 37 20001340
2002 The death domain of NF-kappa B1 p105 is essential for signal-induced p105 proteolysis. The Journal of biological chemistry 36 11976329
2015 NF-κB1 p105 suppresses lung tumorigenesis through the Tpl2 kinase but independently of its NF-κB function. Oncogene 35 26300007
2013 Dietary phytochemicals as potent chemotherapeutic agents against breast cancer: Inhibition of NF-κB pathway via molecular interactions in rel homology domain of its precursor protein p105. Pharmacognosy magazine 35 23661994
2010 Cystatin cures visceral leishmaniasis by NF-κB-mediated proinflammatory response through co-ordination of TLR/MyD88 signaling with p105-Tpl2-ERK pathway. European journal of immunology 35 21182083
2012 An early onset progressive motor neuron disorder in Scyl1-deficient mice is associated with mislocalization of TDP-43. The Journal of neuroscience : the official journal of the Society for Neuroscience 34 23175812
1993 Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhibition of NF-kappa B DNA binding activity. Nucleic acids research 34 7694229
2019 Pathogenesis and biomarkers of natural killer T cell lymphoma (NKTL). Journal of hematology & oncology 33 30876435
2012 Aj-rel and Aj-p105, two evolutionary conserved NF-κB homologues in sea cucumber (Apostichopus japonicus) and their involvement in LPS induced immunity. Fish & shellfish immunology 33 23022054
2009 Immunohistochemical analysis of NF-kappaB signaling proteins IKKepsilon, p50/p105, p52/p100 and RelA in prostate cancers. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 33 19664134
1999 Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105. Oncogene 33 10023675
1990 Multiparameter flow cytometric analysis of neoplasms of the central nervous system: correlation of nuclear antigen p105 and DNA content with clinical behavior. Neurosurgery 33 2377285
2006 Inhibition of Helicobacter hepaticus-induced colitis by IL-10 requires the p50/p105 subunit of NF-kappa B. Journal of immunology (Baltimore, Md. : 1950) 32 17082652
1993 Immunoreactivity of the nuclear antigen p105 is associated with plaques and tangles in Alzheimer's disease. Laboratory investigation; a journal of technical methods and pathology 32 8246448
2006 Defective activation of ERK in macrophages lacking the p50/p105 subunit of NF-kappaB is responsible for elevated expression of IL-12 p40 observed after challenge with Helicobacter hepaticus. Journal of immunology (Baltimore, Md. : 1950) 31 16394015
2015 MiR-31 modulates coelomocytes ROS production via targeting p105 in Vibrio splendidus challenged sea cucumber Apostichopus japonicus in vitro and in vivo. Fish & shellfish immunology 30 25917973
2010 Scyl1 facilitates nuclear tRNA export in mammalian cells by acting at the nuclear pore complex. Molecular biology of the cell 30 20505071
2005 The comet assay to determine the mode of cell death for the ultrasonic delivery of doxorubicin to human leukemia (HL-60 Cells) from Pluronic P105 micelles. Technology in cancer research & treatment 30 16292892
1991 Flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content in advanced gastric cancers. Cancer 30 1913456
2017 Regulation of NF-κB by the p105-ABIN2-TPL2 complex and RelAp43 during rabies virus infection. PLoS pathogens 29 29084252
2009 ABIN-1 negatively regulates NF-kappaB by inhibiting processing of the p105 precursor. Biochemical and biophysical research communications 29 19695220
1993 The activity of a 70 kilodalton I kappa B molecule identical to the carboxyl terminus of the p105 NF-kappa B precursor is modulated by protein kinase A. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 29 8398903
2021 Defining the Role of Nuclear Factor (NF)-κB p105 Subunit in Human Macrophage by Transcriptomic Analysis of NFKB1 Knockout THP1 Cells. Frontiers in immunology 27 34721373
2010 The expression of NAD(P)H:quinone oxidoreductase 1 is increased along with NF-kappaB p105/p50 in human cutaneous melanomas. Oncology reports 27 20204281
1996 Inhibition of p105 processing by NF-kappaB proteins in transiently transfected cells. Oncogene 27 8649779
1996 Elevated serum levels of p105(erbB-2) in patients with advanced-stage prostatic adenocarcinoma. International journal of cancer 27 8900374
2014 IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen. The Journal of experimental medicine 26 25225457
2006 Phosphorylation of NF-kappaB1/p105 by oncoprotein kinase Tpl2: implications for a novel mechanism of Tpl2 regulation. Biochimica et biophysica acta 26 16448710
2016 miRNA expression profiling of Epstein-Barr virus-associated NKTL cell lines by Illumina deep sequencing. FEBS open bio 25 27239439