Affinage

KHDRBS1

KH domain-containing, RNA-binding, signal transduction-associated protein 1 · UniProt Q07666

Length
443 aa
Mass
48.2 kDa
Annotated
2026-06-10
100 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KHDRBS1 (Sam68) is a STAR-family KH-domain RNA-binding protein that couples extracellular and genotoxic signaling to post-transcriptional gene regulation and serves as a multifunctional signaling adaptor (PMID:12478298, PMID:26758068). Its RNA recognition rests on a KH domain embedded in a larger GSG region that binds bipartite U(U/A)AA motifs, and structural work showed STAR proteins engage RNA as homodimers through a dimerization interface essential for splicing activity (PMID:9341174, PMID:19457263, PMID:26758068). A dominant function is signal-responsive alternative splicing: ERK phosphorylation of Sam68 drives CD44 variable-exon inclusion, while it governs Bcl-x splice-site choice, neuronal Sgce exons, cyclin D1b, mTOR, and S6 kinase isoform selection by binding intronic regulatory elements (PMID:12478298, PMID:17371836, PMID:18936165, PMID:20028857, PMID:22424772, PMID:25776557). For several targets Sam68 functions through partner RNA-binding proteins and the spliceosome, recruiting U1 snRNP via its C-terminal YY domain to control 5' splice-site usage and alternative last-exon/3'-end processing, and cooperating with hnRNP A1 (PMID:30767021, PMID:30865884, PMID:17371836, PMID:33537092). Beyond splicing, Sam68 promotes intronic polyadenylation read-through, circRNA biogenesis, cytoplasmic mRNA translation and polysomal recruitment, and nuclear export of intron-containing transcripts (PMID:27845622, PMID:31777926, PMID:19380878, PMID:12482964). As a signaling adaptor it links Src-family and receptor tyrosine kinases to small GTPases, PI3K, the TNF-receptor/NF-κB axis, and PARP1/PAR-dependent DNA-damage responses, and it acts as an RNA-dependent transcriptional coactivator of p53 (PMID:19139276, PMID:11604231, PMID:21620750, PMID:27635653, PMID:27365047). Sam68 activity and localization are controlled by an extensive post-translational code: tyrosine phosphorylation by Fyn, BRK/Sik, and Src; arginine methylation by PRMT1 (reducing RNA binding); acetylation by CBP (enhancing RNA binding); sumoylation by PIAS1; and methylation by Set7/9 (PMID:10564280, PMID:16179349, PMID:10467411, PMID:12529443, PMID:17764653, PMID:15021911, PMID:16568089, PMID:32178870). In vivo, Sam68 knockout produces male infertility, motor-coordination deficits, altered bone/fat differentiation, defective dendritic spine formation, and impaired hepatic gluconeogenesis, reflecting its tissue-specific RNA targets (PMID:19380878, PMID:18325609, PMID:16362077, PMID:23382180, PMID:34099657).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1997 High

    Established that Sam68 is a sequence-specific RNA-binding protein, defining the molecular basis for its post-transcriptional functions.

    Evidence In vitro SELEX and filter-binding with KH-domain mutagenesis identifying a UAAA-containing high-affinity motif

    PMID:9341174

    Open questions at the time
    • Did not establish in vivo targets
    • GSG-region requirement defined but structural basis unknown
  2. 1997 Medium

    Connected Sam68 to receptor signaling by showing it is a phosphorylation substrate and adaptor downstream of T-cell receptor-coupled Src-family kinases.

    Evidence Co-IP and microsequencing in CD3-stimulated T cells linking Sam68 to Fyn, Lck, PLCγ1, PI3K p85, Grb2, SHP-1, Cbl, Jak3

    PMID:9045636

    Open questions at the time
    • Functional consequence of each interaction not dissected
    • Single lab Co-IP
  3. 2000 High

    Showed tyrosine phosphorylation directly toggles Sam68 RNA-binding and nuclear-export functions, linking kinase signaling to its RNA activity.

    Evidence Sik/BRK domain-mapping, in vivo phosphorylation, RNA-binding and Rev-function assays

    PMID:10913193

    Open questions at the time
    • Individual tyrosine sites not mapped in this study
    • Endogenous RNA targets affected not identified
  4. 2002 High

    Demonstrated that Sam68 is an effector of the Ras/ERK pathway in alternative splicing, establishing signal-regulated splicing as a core function.

    Evidence In vitro splicing reconstitution, ERK phosphosite mutagenesis, RNAi knockdown on CD44 v5

    PMID:12478298

    Open questions at the time
    • Mechanism of exon recognition at the spliceosome not resolved
    • Generalization beyond CD44 not shown here
  5. 2003 High

    Identified arginine methylation by PRMT1 as a determinant of Sam68 localization and export activity, adding a second PTM layer.

    Evidence Co-IP, mass spectrometry, PRMT1-deficient cells, HIV RNA export assay

    PMID:12529443

    Open questions at the time
    • Quantitative coupling of methylation to RNA affinity addressed later
    • Interplay with phosphorylation not resolved
  6. 2004 Medium

    Showed CBP acetylation enhances Sam68 RNA binding, providing a positive-regulatory PTM relevant to breast cancer.

    Evidence In vivo acetylation detection, in vitro CBP acetyltransferase and poly(U)-binding assays

    PMID:15021911

    Open questions at the time
    • Acetylated lysine sites not mapped
    • Single lab correlation
  7. 2005 High

    Mapped the specific NLS tyrosines whose BRK phosphorylation drives nuclear export, linking EGF signaling to Sam68 relocalization.

    Evidence Phospho-specific antibodies, immunofluorescence, BRK siRNA, EGF stimulation in breast cancer cells

    PMID:16179349

    Open questions at the time
    • Cytoplasmic functions of exported Sam68 not fully defined here
  8. 2006 Medium

    Established sumoylation by PIAS1 at K96 as a switch between apoptosis promotion and cyclin D1 repression.

    Evidence In vivo sumoylation assay, K96R mutagenesis, SUMO-Sam68 fusion, apoptosis and reporter assays

    PMID:16568089

    Open questions at the time
    • Mechanistic basis of the apoptosis/repression switch unresolved
    • Single lab
  9. 2007 High

    Extended signal-regulated splicing to apoptotic decisions, showing Fyn phosphorylation inverts Sam68 control of Bcl-x splicing.

    Evidence RNAi, overexpression, reciprocal Co-IP with hnRNP A1, mutagenesis

    PMID:17371836

    Open questions at the time
    • Stoichiometry/cooperation with hnRNP A1 not fully defined
  10. 2009 High

    Defined Sam68 as a master regulator of developmental and cell-fate splicing programs across neurogenesis, with parallel adaptor roles at the plasma membrane controlling GTPase signaling and migration.

    Evidence Splicing-sensitive microarrays and minigenes (Sgce); Sam68 KO MEFs, TIRF, Rho/Rac assays; complex equilibrium MS/SEC; KO mouse spermatogenesis polysome studies

    PMID:18936165 PMID:19139276 PMID:19380878 PMID:19762470

    Open questions at the time
    • How a single protein selects distinct target sets per tissue unresolved
    • Composition of the >1 MDa RNP only partially defined
  11. 2009 Medium

    Refined the RNA-recognition code, showing a bipartite U(U/A)AA requirement and that RG repeats confer nonspecific RNA binding.

    Evidence SELEX and binding assays (bipartite motif); chimeric protein and RG-region transfer experiments

    PMID:11395494 PMID:19457263

    Open questions at the time
    • In vivo prevalence of bipartite sites not surveyed
    • Single lab biochemistry
  12. 2012 High

    Linked Sam68-controlled splicing to metabolic differentiation, with intron retention of mTOR explaining adipogenic defects.

    Evidence Sam68 KO mice, CLIP, minigenes, rescue with mTOR cDNA

    PMID:22424772

    Open questions at the time
    • Direct spliceosomal mechanism at intron 5 resolved only later
  13. 2013 High

    Established a translational/dendritic function: Sam68 delivers actb mRNA to synaptic polysomes to support spine formation.

    Evidence Sam68 KO mice, RNAi, synaptic polysome fractionation, spine morphology and electrophysiology

    PMID:23382180

    Open questions at the time
    • Mechanism of dendritic mRNA transport not detailed
    • Other synaptic mRNA cargoes not enumerated
  14. 2016 High

    Revealed direct roles in the DNA-damage response — as a PARP1 partner enabling PAR/NF-κB anti-apoptotic signaling and as an RNA-dependent p53 transcriptional coactivator.

    Evidence Sam68 KO cells/mice with PARP1 Co-IP and PAR assays; CRISPR isogenic p53 lines with Co-IP and ChIP; intronic polyadenylation control of Aldh1a3 in NPCs

    PMID:27365047 PMID:27458801 PMID:27635653 PMID:27845622

    Open questions at the time
    • Direct vs indirect recruitment to lesions not fully separated
    • RNA dependence of p53 coactivation not molecularly defined
  15. 2016 High

    Provided the structural basis for STAR-family RNA recognition, showing homodimerization enables transcriptome target selection.

    Evidence X-ray/NMR structures of Sam68/T-STAR with RNA and dimerization-interface mutagenesis plus splicing minigenes

    PMID:26758068

    Open questions at the time
    • Structural impact of PTMs on dimer/RNA binding not modeled
  16. 2019 High

    Defined the spliceosomal mechanism, showing Sam68 recruits U1 snRNP via its YY domain to enforce 5' splice-site usage and suppress premature termination/polyadenylation.

    Evidence Co-IP/domain mapping, minigenes and mutagenesis on mTOR intron 5; Sam68 KO mice with RNA-seq and U1snRNP Co-IP for ALE usage in meiosis

    PMID:30767021 PMID:30865884

    Open questions at the time
    • Generality of U1 recruitment across all Sam68 targets not established
  17. 2021 High

    Extended Sam68 to protein-stability control of metabolism, stabilizing CRTC2 to drive hepatic gluconeogenesis.

    Evidence Global and hepatocyte-specific KO mice, Co-IP, ubiquitination assay, truncation mutants, glucose tolerance tests

    PMID:34099657

    Open questions at the time
    • Whether CRTC2 stabilization is RNA-dependent unclear
    • Direct deubiquitinase coupling not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the combinatorial PTM code, dimerization state, and complex equilibrium together select which RNA targets or signaling outputs Sam68 engages in a given cell type remains unresolved.
  • No integrated model linking PTM state to target choice
  • Cell-type-specific cofactor logic undefined
  • Structural effect of PTMs on the dimer interface unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 10 GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0045182 translation regulator activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 6 GO:0005634 nucleus 5 GO:0005654 nucleoplasm 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-8953854 Metabolism of RNA 10 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-73894 DNA Repair 3
Partners
CREBBPFYNHNRNPA1PARP1PRMT1PTK6SNRNP70TP53
Complex memberships
TNF receptor complex IU1 snRNP-associated splicing complexcaspase-8-FADD complex IIcytoplasmic stress granules

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Sam68 is a direct substrate of ERK (extracellular signal-regulated kinase) and binds exonic splice-regulatory elements of the CD44 v5 exon. ERK phosphorylation of Sam68 stimulates inclusion of the v5 exon in vitro, and forced Sam68 expression enhanced ERK-mediated v5 inclusion; mutation of ERK phosphorylation sites in Sam68 impaired this enhancement. Suppression of Sam68 abolished Ras-pathway-induced alternative splicing of endogenous CD44-v5. In vitro splicing assay, site-directed mutagenesis of ERK phosphorylation sites, forced expression and RNAi knockdown, RNA binding assays Nature High 12478298
2007 Sam68 binds the Bcl-x mRNA and promotes inclusion of the proapoptotic Bcl-x(s) splice site. Depletion of Sam68 by RNAi caused accumulation of antiapoptotic Bcl-x(L), while up-regulation increased Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn kinase inverted this effect, favoring Bcl-x(L) splice site selection. Sam68 interacted with hnRNP A1, and depletion of hnRNP A1 or mutations impairing this interaction attenuated Bcl-x(s) splicing. A point mutation in the RNA-binding domain influenced both splicing activity and subnuclear localization. RNAi knockdown, overexpression, Co-IP, site-directed mutagenesis, immunofluorescence The Journal of cell biology High 17371836
2003 PRMT1 (protein arginine N-methyltransferase 1) associates with and methylates Sam68 in vivo, introducing asymmetrical dimethylarginines near the proline motif P3. Deletion of methylation sites or use of methylase inhibitors caused Sam68 accumulation in the cytoplasm. PRMT1-deficient embryonic stem cells also showed cytoplasmic Sam68. Methylase inhibition prevented Sam68-mediated export of unspliced HIV RNAs. Co-IP, mass spectrometry, methylation-specific antibody, inhibitor treatment, PRMT1-deficient cells, HIV RNA export assay Molecular biology of the cell High 12529443
1997 Sam68 binds RNA with specificity and high affinity via a KH domain embedded in a larger GSG domain. SELEX identified high-affinity RNA sequences (Kd ~12–40 nM) containing a UAAA motif; mutation of UAAA to UACA abolished binding. The KH domain alone was insufficient; the broader GSG region was required. KH domain mutations analogous to loss-of-function mutations in FMR1 and GLD-1 abolished RNA binding. In vitro SELEX, filter-binding affinity assays, site-directed mutagenesis of KH domain The Journal of biological chemistry High 9341174
2000 Sik (mouse) / BRK (human) tyrosine kinase associates with Sam68 through its SH3 and SH2 domains, binding the proline-rich P3 region of Sam68. Sik phosphorylates Sam68 in the nucleus and abolishes Sam68's ability to bind RNA and act as a cellular Rev homologue (facilitating intron-containing RNA export). Co-IP, domain-deletion mapping, in vivo phosphorylation, RNA-binding assay, Rev-function assay Molecular and cellular biology High 10913193
1999 The Src family kinase Fyn mediates tyrosine phosphorylation of Sam68, which negatively regulates Sam68 association with the nuclear splicing-associated factor YT521-B. Overexpression of Fyn dissolves nuclear dots containing YT521-B and Sam68. Fyn-phosphorylated Sam68 no longer colocalizes with YT521-B. Co-IP, immunofluorescence colocalization, Fyn overexpression, deletion analysis Molecular biology of the cell Medium 10564280
1997 Sam68 associates with Fyn and Lck (Src family kinases) in T cells via their SH2 and SH3 domains. CD3 cross-linking induces tyrosine phosphorylation of Sam68, and Sam68 is coimmunoprecipitated with PLCγ1, PI3K p85, Grb2, SHP-1, Cbl, and Jak3, indicating an adaptor function downstream of TCR-coupled kinases. Co-IP, purification and microsequencing, T cell stimulation assays The Journal of biological chemistry Medium 9045636
2005 BRK phosphorylates Sam68 on all three tyrosines in its nuclear localization signal (NLS), including the principal site Y440. This phosphorylation induces relocalization of Sam68 from the nucleus to non-nuclear compartments. EGF treatment in breast cancer cells promotes Sam68 phosphorylation at Y440 in a BRK-dependent manner (reversed by BRK siRNA). Sam68 overexpression suppresses BRK-induced cell proliferation. Phospho-specific antibodies, indirect immunofluorescence, BRK siRNA, EGF stimulation, site-directed mutagenesis The Journal of biological chemistry High 16179349
2009 Sam68 is required for polysomal recruitment of specific mRNAs in male germ cells and for accumulation of the corresponding proteins. Sam68(-/-) male mice are infertile with defects in spermatogenesis. Sam68 associates with polyadenylated mRNAs in the cytoplasm during meiotic divisions and in round spermatids, interacting with the translational machinery. Sam68 knockout mice, polysome fractionation, RNA immunoprecipitation, heterologous translation system The Journal of cell biology High 19380878
2009 Sam68 is required for alternative splicing of a set of exons during neurogenesis. Sam68 represses an exon in epsilon sarcoglycan (Sgce) through RNA-binding activity and intronic RNA elements. Sam68 protein is upregulated upon neuronal differentiation of P19 cells; Sam68 knockdown prevents neuronal differentiation of both P19 cells and primary neural progenitor cells, while overexpression promotes it. RNAi knockdown, splicing-sensitive microarrays, minigene assays, mutagenesis, shRNA in primary cells Molecular and cellular biology High 18936165
2012 Sam68 regulates alternative splicing of the mTOR transcript during adipogenesis by binding intronic splice elements in mTOR intron 5 required for 5' splice site usage. Sam68(-/-) adipocytes retain intron 5, introducing a premature stop codon that destabilizes mTOR mRNA, reducing mTOR levels, S6 and Akt phosphorylation, and adipogenic differentiation. Exogenous full-length mTOR rescues the adipogenesis defect. Sam68 KO mice, genome-wide exon profiling, CLIP, minigene assays, rescue with mTOR cDNA Molecular cell High 22424772
2009 Sam68 enhances alternative splicing of cyclin D1b by binding the proximal region of CCND1 intron 4; this binding inversely correlates with recruitment of spliceosomal component U1-70K. Sam68 is recruited to the CCND1 gene (shown by ChIP) and binds cyclin D1 mRNA (shown by RIP). Phosphorylation of Sam68 by signal transduction pathways modulates its affinity for CCND1 intron 4 and splicing activity. ChIP, RNA co-IP, RNAi, overexpression, minigene reporter assay, phospho-mutant analysis Cancer research High 20028857
2011 Sam68 acts as a signaling adaptor at the TNF receptor complex I, where it facilitates RIP recruitment, ubiquitylation of RIP, cIAP1 recruitment, and TRAF2 maintenance, enabling TAK1-IKK kinase complex activation and NF-κB signaling. Sam68 is also part of the cytoplasmic caspase-8-FADD complex II; RIP recruitment and caspase activation are absent in Sam68 KO cells. Sam68 KO cells, Co-IP, ubiquitylation assays, kinase complex activation assays Molecular cell High 21620750
2004 Sam68 is acetylated in vivo in human mammary epithelial cell lines, with highest acetylation in tumorigenic breast cancer lines. The acetyltransferase CBP acetylates Sam68 in vitro and enhances its binding to poly(U) RNA. Sam68 acetylation positively correlates with its RNA-binding activity. In vivo acetylation detection, in vitro acetyltransferase assay with CBP, RNA-binding assays Oncogene Medium 15021911
2006 Sam68 is modified by SUMO, with PIAS1 acting as the E3 SUMO ligase. Lysine 96 is the major SUMO acceptor site. Mutation of K96 to arginine enhanced Sam68-induced apoptosis but inhibited its transcriptional repression of cyclin D1. A SUMO-1-Sam68 fusion inhibited apoptosis but strongly repressed cyclin D1 expression. In vivo sumoylation assay, PIAS1 co-expression, K96R mutagenesis, SUMO fusion protein, reporter assay, apoptosis assay Oncogene Medium 16568089
2007 Arginine methylation of Sam68's RG-repeat regions by PRMT1 markedly reduces poly(U) RNA binding ability in vitro. The RG repeats of Sam68 directly bind poly(U); arginine methylation of these repeats abrogates binding. Overexpression of PRMT1 in cells increases Sam68 arginine methylation and decreases its poly(U) binding. In vitro methylation and RNA-binding assays, PRMT1 overexpression, methylation-binding correlation Archives of biochemistry and biophysics Medium 17764653
2001 Sam68 functions as a docking protein linking p120GAP and PI3K in insulin receptor signaling. Insulin stimulation promotes Sam68 relocalization from nucleus to cytoplasm; tyrosine-phosphorylated Sam68 co-precipitates with p85 PI3K, IRS-1, and IR. Sam68 also associates with p120GAP after tyrosine phosphorylation by the IR, with this association mediated by GAP's SH2 domains. PI3K activity is increased in both anti-Sam68 and anti-GAP immunoprecipitates upon insulin stimulation. Co-immunoprecipitation, subcellular fractionation, PI3K activity assay, insulin receptor stimulation Molecular and cellular endocrinology Medium 11604231
2005 Sam68(-/-) mice exhibit motor coordination defects: Sam68-null mice show more hindpaw faults in beam walking and fall from rotorod at lower speeds. Sam68 is highly expressed in the cerebellum, implicating it in motor coordination circuitry. Sam68 KO mice, behavioral assays (beam walking, rotorod, balance test) Behavioural brain research Medium 18325609
2005 Sam68(-/-) mice show age-related protection from bone loss. Sam68-null bone marrow stromal cells have a differentiation advantage toward osteoblasts, and Sam68 knockdown in C3H10T1/2 cells promotes osteocalcin expression after BMP-2 induction. Sam68(-/-) MEFs show impaired adipocyte differentiation. Thus Sam68 is a positive regulator of adipocyte differentiation and negative regulator of osteoblast differentiation. Sam68 KO mice, shRNA knockdown, differentiation assays, histology PLoS genetics Medium 16362077
2005 Sam68 translocates to the cytoplasm and associates with polysomes in mouse pachytene spermatocytes during meiotic divisions. This translocation correlates with serine/threonine phosphorylation and is blocked by ERK1/2 and cyclin B-cdc2 inhibitors. Both kinases associate with Sam68 in pachytene spermatocytes and phosphorylate regions flanking the RNA-binding motif. Subcellular fractionation, polysome sedimentation, kinase inhibitors, Co-IP with ERK and cyclin B-cdc2 Molecular biology of the cell Medium 16221888
2004 In hippocampal neurons, Sam68 undergoes activity-responsive translocation from nucleus to dendrites following KCl depolarization. Translocation requires calcium channel activity (blocked by nimodipine), is microtubule-dependent, and is partially blocked by CRM1 inhibitor leptomycin B. A fraction of dendritic GFP-Sam68 colocalizes with RNA clusters. The Sam68 N-terminus is required for nuclear retention. GFP-Sam68 live-cell imaging, calcium channel inhibitor, microtubule inhibitor, leptomycin B, RNA staining Journal of cell science Medium 14996936
2013 Sam68 knockdown in hippocampal neurons decreases the amount of β-actin (actb) mRNA in the synaptodendritic compartment and results in fewer dendritic spines. Sam68-KO mice have reduced levels of actb mRNA associated with synaptic polysomes and diminished synaptic β-actin protein. Genetic knockout or acute knockdown in vivo results in fewer excitatory synapses. Disruption of Sam68-actb mRNA binding phenocopies Sam68 knockdown. Sam68 KO mice, RNAi knockdown, synaptic polysome fractionation, spine morphology analysis, electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 23382180
1999 Sam68's proline-rich motifs function as specific SH3 domain binding sites; the Src SH3 domain directs binding to an N-terminal proline motif of Sam68 (residues 38–45), and this SH3-mediated docking facilitates phosphorylation of Sam68 tyrosines by the Src kinase domain. Mutation of the Src SH3 binding site on Sam68, or addition of corresponding peptides, inhibits Src phosphorylation of Sam68 in vitro. In vitro SH3 domain binding, synthetic peptide competition, site-directed mutagenesis, in vitro kinase assay Oncogene Medium 10467411
2002 Sam68 physically interacts with CBP through the CBP CH3 domain, in part through a conserved FXD/EXXXL motif. Sam68 and CBP interact in vivo and colocalize in nuclear sub-domains. Sam68 has transcriptional repression activity independent of its RNA-binding activity. Co-IP, domain mapping, transcriptional reporter assay, immunofluorescence colocalization Molecular cancer research Medium 12496368
2009 Sam68-deficient cells exhibit sustained Src activity after cell attachment, leading to constitutive tyrosine phosphorylation and activation of p190RhoGAP and its association with p120rasGAP, and deregulated RhoA and Rac1 activity. Sam68 localizes near the plasma membrane after cell attachment (TIRF microscopy), coinciding with phosphorylation of its C-terminal tyrosines and association with Csk. Loss of Sam68 impairs cell polarity and migration. Sam68 KO MEFs, TIRF microscopy, Co-IP, phospho-specific antibodies, Rho GTPase activity assays Molecular and cellular biology High 19139276
2009 Sam68 exists in equilibrium between a large (>1 MDa) ribonucleoprotein complex (~40 proteins, RNA-dependent) and a smaller (200–450 kDa) complex in HeLa cells. EGF or PMA treatment dissociates Sam68 from the large complex, shifting it to the smaller complex. The appearance of Sam68 in the small complex correlates with its ability to promote CD44 alternative splicing and cell migration. Immunoprecipitation-mass spectrometry, size-exclusion chromatography, RNase treatment, EGF/PMA stimulation, splicing assay The Journal of biological chemistry Medium 19762470
2016 Sam68 deficiency abolishes DNA damage-stimulated poly(ADP-ribose) (PAR) production. Sam68 is recruited to DNA lesions and directly interacts with PARP1; this interaction is required for PARP1-mediated PAR production. Sam68-deleted cells and mice are hypersensitive to DNA-damaging agents. Sam68 is also required for NF-κB transactivation of anti-apoptotic genes downstream of PAR production. Sam68 KO cells and mice, biochemical fractionation, Co-IP, PAR production assays, DNA damage sensitivity assays PLoS biology High 27635653
2016 Sam68 is required for genotoxic stress-initiated NF-κB activation through PAR-dependent signaling in colon cancer. Sam68 deletion abolishes DNA damage-stimulated PAR production and PAR-dependent NF-κB transactivation of anti-apoptotic genes; Sam68-deleted cells are hypersensitive to genotoxic stress. Sam68 upregulation in colon cancer coincides with elevated PAR production and NF-κB-mediated anti-apoptotic transcription. Sam68 KO cells and mice, genotoxic stress assays, PAR production assays, tumor burden assays eLife Medium 27458801
2016 Sam68 promotes self-renewal of neural progenitor cells (NPCs) by binding an intronic polyadenylation site in Aldh1a3 pre-mRNA, preventing premature transcript termination and favoring expression of functional ALDH1A3 enzyme. Khdrbs1 KO NPCs show lower ALDH1A3 expression and activity, reduced glycolysis, and depleted embryonic NPC pool. Khdrbs1 KO mice, 3'-end processing assays, CLIP, minigene polyadenylation assay, metabolic assays eLife High 27845622
2016 Sam68 acts as a transcriptional coactivator of p53 in response to DNA damage. Sam68 physically interacts with p53 in an RNA-dependent manner; this interaction is essential for coactivator function. Both Sam68 and p53 are recruited to promoters of p53-responsive genes. Sam68 depletion causes defects in DNA damage-induced cell cycle arrest and apoptosis mediated by p53. CRISPR/Cas9 KO cell lines (isogenic p53 WT vs KO), Co-IP, ChIP, reporter assays, cell cycle and apoptosis assays Nucleic acids research High 27365047
2018 SAM68 (KHDRBS1) is required for NORAD lncRNA function in antagonizing Pumilio. SAM68 interacts with NORAD, and this interaction is required for NORAD-mediated antagonism of Pumilio repressors; the interaction provides a paradigm for how repeated elements in a lncRNA facilitate function through an RNA-binding protein. Co-IP/RNA-IP, functional NORAD assays, SAM68 knockdown Genes & development Medium 29386330
2019 Sam68 binds Alu-rich intronic sequences in the SMN pre-mRNA (shown by CLIP), promoting widespread alternative circular RNA (circRNA) biogenesis. Mutagenesis of Sam68 binding sites in SMN IRAlus and Sam68 silencing reduce circRNA formation in vitro and in vivo. CLIP, mutagenesis, Sam68 silencing, circRNA detection assays Nucleic acids research Medium 31777926
2019 Sam68 interacts with U1A (core component of U1 snRNP) through its C-terminal tyrosine-rich (YY) domain, and this interaction promotes U1 snRNP recruitment to the 5' splice site of mTOR intron 5. Deletion of the U1A-SAM68 interaction domain or mutation of SAM68 binding sites in mTOR intron 5 abrogates U1A recruitment and 5' splice site recognition, causing premature termination and polyadenylation. Co-IP, domain mapping, minigene assays, mutagenesis, U1A knockdown Nucleic acids research High 30767021
2019 Sam68 cooperates with U1snRNP to regulate alternative last exon (ALE) usage during male meiosis. Loss of Sam68 preferentially causes premature transcript termination at internal polyadenylation sites. Sam68 physically associates with U1snRNP, and U1snRNP recruitment to Sam68-regulated ALEs is impaired in Sam68(-/-) germ cells. Sam68 KO mice, RNA-seq, Co-IP of Sam68 and U1snRNP, splicing/polyadenylation assays Cell reports High 30865884
2015 Sam68 regulates isoform expression of S6 kinase (Rps6kb1) during adipogenesis. Sam68 binds RNA encoded by Rps6kb1 intron 6 (shown by CLIP) and prevents SRSF1-mediated alternative splicing that generates inhibitory p31S6K1. Sam68-deficient adipocytes express p31S6K1, inhibiting adipogenesis; depletion of p31S6K1 partially restores adipogenesis. CLIP, minigene assays, siRNA, Sam68 KO adipocytes, p31S6K1 overexpression Molecular and cellular biology High 25776557
2015 SMAR1 negatively regulates Sam68's splicing activity through HDAC6-mediated deacetylation of Sam68. SMAR1 maintains Sam68 in a deacetylated (less active) state via HDAC6. ERK-mediated phosphorylation of SMAR1 (at T345 and T360) localizes SMAR1 to the cytoplasm, releases the inhibitory SMAR1-HDAC6-Sam68 complex, and facilitates Sam68 acetylation and alternative splicing of CD44 variant exons. Co-IP, knockdown, HDAC6 inhibition, phosphomimetic mutagenesis, CD44 minigene reporter, in vivo tail-vein injection model Proceedings of the National Academy of Sciences of the United States of America High 26080397
2016 The methyltransferase Set7/9 (KMT7) co-immunoprecipitates with Sam68 and methylates Sam68 on K208. Knockout of Set7/9 decreases Sam68 protein levels in cells, resulting in altered cell cycle and apoptosis regulation. The RG-rich domain of Sam68 mediates the interaction with Set7/9's MORN domain. Pull-down, Co-IP, in vitro methylation assay, Set7/9 KO cells Biochemical and biophysical research communications Medium 32178870
2021 Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination, thereby stabilizing CRTC2 protein levels. Sam68 promotes hepatic gluconeogenesis: global and hepatic Sam68 deletion significantly reduces blood glucose and glucagon-induced gluconeogenic gene expression. Sam68 truncation mutants lacking C-terminal (Sam68ΔC) or N-terminal (Sam68ΔN) domains respectively fail to bind CRTC2 or to stabilize CRTC2 protein. Sam68 global and hepatocyte-specific KO mice, Co-IP, ubiquitination assay, truncation mutagenesis, glucose tolerance tests Nature communications High 34099657
2021 SAM68 promotes aerobic glycolysis and lung adenocarcinoma tumorigenesis by mediating alternative splicing of pyruvate kinase (PKM) pre-mRNA to favor PKM2 over PKM1. Mechanistically, SAM68 binds the 351–443 aa region to the RGG motif of hnRNP A1, enhancing hnRNP A1 binding to PKM exon 9 and promoting PKM2 formation. RNA-IP, Western blot, minigene splicing assays, domain mapping, in vitro and in vivo tumor models Theranostics Medium 33537092
2008 Sam68 interacts with the androgen receptor (AR) in vivo in LNCaP prostate cancer cells and is dynamically recruited to androgen response elements within the PSA gene promoter (by ChIP). Wild-type Sam68 and an RNA-binding-impaired mutant (V229F) both function as ligand-dependent AR co-activators in reporter assays. Conversely, Sam68-mediated splicing of a Sam68-responsive exon under androgen-responsive promoter control is strongly repressed by AR/androgens and reversed by Sam68 expression; V229F Sam68 enhances this splicing repression, demonstrating separable transcriptional co-activation and splicing functions. Co-IP, ChIP, luciferase reporter assay, minigene splicing assay, V229F mutagenesis The Journal of pathology Medium 18273831
2015 Sam68 controls expression of AR-V7 splice variant in an RNA-binding-dependent manner using a minigene reporter for exon 3b inclusion. Sam68 directly interacts with AR-V7 protein through a shared domain with full-length AR. Sam68 co-activates ligand-independent AR-V7 transcriptional activity in an RNA-binding-independent manner and controls expression of the AR-V7 target gene UBE2C. Minigene reporter assay, Co-IP, luciferase reporter assay, RNAi knockdown, Western blot Scientific reports Medium 26310125
2016 Sam68 binds Alu-rich intronic sequences in the SMN pre-mRNA and promotes circRNA biogenesis. The crystal/NMR structure of T-STAR and Sam68 in complex with RNA established that STAR proteins bind RNA as homodimers through an unexpected dimerization interface distinct from other STAR family members; this dimerization interface is crucial for splicing regulatory activity, and increased RNA affinity through dimer formation enables target selection within the transcriptome. X-ray crystallography, NMR, RNA-binding assays, splicing minigene assays with dimerization-interface mutants Nature communications High 26758068
2009 Sam68 binds bipartite RNA motifs consisting of direct U(U/A)AA repeats, requiring both half-sites for high-affinity binding; this bipartite requirement was demonstrated by SELEX and confirmed for Sam68, SLM-2, QKI, and GLD-1. SELEX, filter-binding assays, mutant RNA probes BMC molecular biology Medium 19457263
2001 Sam68 contains two arginine-glycine (RG)-rich regions that confer nonspecific RNA binding to its GSG domain. A minimal 26-aa RG-rich sequence from Sam68 is sufficient to confer homopolymeric RNA binding to the GSG domain of QKI-7 (a different STAR protein) and to enable it to functionally substitute for HIV-1 Rev in RNA nuclear export. Domain-deletion analysis, chimeric protein construction, RNA-binding assay, HIV Rev reporter assay The Journal of biological chemistry Medium 11395494
2002 Sam68 enhances cytoplasmic utilization (translation) of CTE-containing intron-containing mRNA by ~60–70-fold at the protein level with only modest effect on cytoplasmic RNA levels, demonstrating a post-export translational enhancement function. An RNA-binding-deficient Sam68 mutant (G178E) does not enhance CTE function. Activated Sik/BRK (which hyperphosphorylates Sam68) inhibits this activity in a dose-dependent manner. Reporter gene expression assay, RNA analysis, Sik/BRK co-expression, G178E point mutant Molecular and cellular biology Medium 12482964
2010 Sam68 is sequestered by CGG repeat-expanded RNA in FXTAS, losing its splicing-regulatory function. Sam68 is recruited first among RNA-binding proteins to CGG repeat aggregates. Regulation of Sam68 tyrosine phosphorylation modulates its localization within CGG aggregates. Tautomycin prevents both Sam68 and CGG RNA aggregate formation. Fluorescence imaging of intranuclear aggregates, splicing assays in patient cells, phosphorylation modulation experiments, tautomycin treatment The EMBO journal Medium 20186122
2012 FMDV 3C protease cleaves Sam68 at its C-terminus (which contains the NLS), causing redistribution of Sam68 to the cytoplasm. Sam68 interacts with the FMDV IRES within the 5' non-translated region and its knockdown decreases FMDV IRES-driven translation activity and reduces viral titers by 1000-fold. siRNA knockdown, IRES reporter assay, protease cleavage assay, viral titer measurement Virology Medium 22280896
2019 c-MYC directly binds to and activates the Sam68 (KHDRBS1) gene promoter, and also affects productive splicing of the nascent Sam68 transcript by modulating transcriptional elongation rate. Sam68 and c-MYC levels positively correlate in prostate cancer patients. c-MYC-dependent Sam68 expression is under control of external cues (androgens, mitogens). ChIP, promoter reporter assay, transcriptional elongation assay, patient data correlation, androgen/mitogen stimulation Nucleic acids research Medium 31066450
2009 Sam68 cytoplasmic mutants suppress HIV-1 Nef expression by inducing stress granules and sequestering nef mRNA in those granules. Domain aa269–321 and the KH domain are required for stress granule induction. Nef suppression is specific, conferred by Sam68 binding to nef mRNA 3'UTR. Sam68 cytoplasmic mutant expression, stress granule imaging, mRNA localization assay, domain deletion Molecular cell Medium 19150430
2009 Sam68 is recruited to cytoplasmic stress granules under oxidative stress by complexing with the core stress granule component TIA-1. Both domain aa269–321 and the KH domain are essential for Sam68 stress granule recruitment. Sam68 knockdown has no effect on stress granule assembly, showing Sam68 is not a constitutive SG component. Immunofluorescence, Co-IP with TIA-1, domain deletion mutants, Sam68 knockdown Experimental cell research Medium 19615357
2002 Sam68 forms a complex with the HIV-1 Rev protein; mutagenesis identified residues 321–410 of Sam68 as directly involved in Rev binding, and Rev double mutation L78D/E79L eliminated binding to Sam68. Sam68 expression promotes Rev nuclear export; down-modulation of Sam68 causes nuclear retention and colocalization of Rev and CRM1, demonstrating involvement in CRM1-mediated Rev nuclear export. Mutagenesis, Co-IP, antisense knockdown, digital fluorescence microscopy, Rev-dependent reporter assay Journal of virology Medium 11932418

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Signal-dependent regulation of splicing via phosphorylation of Sam68. Nature 383 12478298
2010 Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. The EMBO journal 305 20186122
2007 The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x. The Journal of cell biology 270 17371836
2003 Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1. Molecular biology of the cell 223 12529443
2003 Sam68, the KH domain-containing superSTAR. Biochimica et biophysica acta 221 14643926
1999 The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn). Molecular biology of the cell 167 10564280
2007 The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells. Oncogene 152 17237817
1997 Specificity and determinants of Sam68 RNA binding. Implications for the biological function of K homology domains. The Journal of biological chemistry 150 9341174
1996 Human protein Sam68 relocalization and interaction with poliovirus RNA polymerase in infected cells. Proceedings of the National Academy of Sciences of the United States of America 144 8637866
2009 Alternative splicing of the cyclin D1 proto-oncogene is regulated by the RNA-binding protein Sam68. Cancer research 140 20028857
2011 The RNA-binding protein Sam68 is a multifunctional player in human cancer. Endocrine-related cancer 136 21565971
2000 Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability. Molecular and cellular biology 135 10913193
2018 The long non-coding RNA CYTOR drives colorectal cancer progression by interacting with NCL and Sam68. Molecular cancer 120 30064438
2009 Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. The Journal of cell biology 119 19380878
2005 Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression. The Journal of biological chemistry 110 16179349
2005 Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss. PLoS genetics 109 16362077
1999 T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis. Human molecular genetics 97 10332027
2012 The Sam68 STAR RNA-binding protein regulates mTOR alternative splicing during adipogenesis. Molecular cell 95 22424772
2008 Sam68 regulates a set of alternatively spliced exons during neurogenesis. Molecular and cellular biology 95 18936165
1997 Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling. The Journal of biological chemistry 93 9045636
2003 Sam68 enhances the cytoplasmic utilization of intron-containing RNA and is functionally regulated by the nuclear kinase Sik/BRK. Molecular and cellular biology 92 12482964
2010 Sam68 up-regulation correlates with, and its down-regulation inhibits, proliferation and tumourigenicity of breast cancer cells. The Journal of pathology 90 20662004
1999 Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis. Proceedings of the National Academy of Sciences of the United States of America 90 10077576
2015 SAM68: Signal Transduction and RNA Metabolism in Human Cancer. BioMed research international 81 26273626
2004 The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activity. Oncogene 75 15021911
2012 The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells. Virology 74 22280896
2000 Sam68, RNA helicase A and Tap cooperate in the post-transcriptional regulation of human immunodeficiency virus and type D retroviral mRNA. Oncogene 73 10951562
2011 Sam68 is required for both NF-κB activation and apoptosis signaling by the TNF receptor. Molecular cell 71 21620750
2005 The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysomes in mouse spermatocytes. Molecular biology of the cell 71 16221888
2011 Fyn requires HnRNPA2B1 and Sam68 to synergistically regulate apoptosis in pancreatic cancer. Carcinogenesis 69 21642356
2007 Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis. Oncogene 69 17621265
2009 The STAR RNA binding proteins GLD-1, QKI, SAM68 and SLM-2 bind bipartite RNA motifs. BMC molecular biology 66 19457263
2008 The RNA-binding and adaptor protein Sam68 modulates signal-dependent splicing and transcriptional activity of the androgen receptor. The Journal of pathology 65 18273831
2004 Sam68 exerts separable effects on cell cycle progression and apoptosis. BMC cell biology 64 14736338
2006 SUMO modification of Sam68 enhances its ability to repress cyclin D1 expression and inhibits its ability to induce apoptosis. Oncogene 63 16568089
1997 The SH3 domain of Bruton's tyrosine kinase interacts with Vav, Sam68 and EWS. Scandinavian journal of immunology 61 9201297
2016 Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68. Nature communications 60 26758068
2002 Direct participation of Sam68, the 68-kilodalton Src-associated protein in mitosis, in the CRM1-mediated Rev nuclear export pathway. Journal of virology 60 12134041
2002 Identification of cellular mRNA targets for RNA-binding protein Sam68. Nucleic acids research 60 12490714
2005 Sam68 is absolutely required for Rev function and HIV-1 production. Nucleic acids research 59 15701759
2020 Sam68 binds Alu-rich introns in SMN and promotes pre-mRNA circularization. Nucleic acids research 57 31777926
2018 SAM68 is required for regulation of Pumilio by the NORAD long noncoding RNA. Genes & development 56 29386330
2016 Sam68 promotes self-renewal and glycolytic metabolism in mouse neural progenitor cells by modulating Aldh1a3 pre-mRNA 3'-end processing. eLife 55 27845622
2005 Role of Sam68 as an adaptor protein in signal transduction. Cellular and molecular life sciences : CMLS 55 15619005
2015 The RNA-binding protein Sam68 regulates expression and transcription function of the androgen receptor splice variant AR-V7. Scientific reports 53 26310125
2000 Neoplastic transformation and tumorigenesis associated with sam68 protein deficiency in cultured murine fibroblasts. The Journal of biological chemistry 52 11032831
2013 Role of Sam68 in post-transcriptional gene regulation. International journal of molecular sciences 50 24287914
2016 Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation. eLife 49 27458801
2002 Expression of exogenous Sam68, the 68-kilodalton SRC-associated protein in mitosis, is able to alleviate impaired Rev function in astrocytes. Journal of virology 49 11932418
2013 RNA-binding protein Sam68 controls synapse number and local β-actin mRNA metabolism in dendrites. Proceedings of the National Academy of Sciences of the United States of America 47 23382180
2015 Nuclear matrix-associated protein SMAR1 regulates alternative splicing via HDAC6-mediated deacetylation of Sam68. Proceedings of the National Academy of Sciences of the United States of America 43 26080397
2008 Motor coordination defects in mice deficient for the Sam68 RNA-binding protein. Behavioural brain research 43 18325609
2012 Mechanisms of HGF/Met signaling to Brk and Sam68 in breast cancer progression. Hormones & cancer 41 22124844
2009 An adaptor role for cytoplasmic Sam68 in modulating Src activity during cell polarization. Molecular and cellular biology 41 19139276
2001 Sam68 is a docking protein linking GAP and PI3K in insulin receptor signaling. Molecular and cellular endocrinology 41 11604231
2019 The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing. Cancers 40 31450747
2002 Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68. Molecular cancer research : MCR 40 12496368
2010 Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. Human molecular genetics 39 20881015
2007 Arginine methylation of Sam68 and SLM proteins negatively regulates their poly(U) RNA binding activity. Archives of biochemistry and biophysics 39 17764653
2022 ebv-circRPMS1 promotes the progression of EBV-associated gastric carcinoma via Sam68-dependent activation of METTL3. Cancer letters 37 35304258
2019 Functional Interaction between U1snRNP and Sam68 Insures Proper 3' End Pre-mRNA Processing during Germ Cell Differentiation. Cell reports 37 30865884
2009 Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration. Molecular cell 37 19150430
2015 Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation. Journal of virology 36 26202240
2019 c-MYC empowers transcription and productive splicing of the oncogenic splicing factor Sam68 in cancer. Nucleic acids research 35 31066450
2011 Hsp22 (HspB8/H11) knockdown induces Sam68 expression and stimulates proliferation of glioblastoma cells. Journal of cellular physiology 35 21678403
2004 RACK1 regulates Src-mediated Sam68 and p190RhoGAP signaling. Oncogene 34 15184885
2018 hnRNP A1/A2 and Sam68 collaborate with SRSF10 to control the alternative splicing response to oxaliplatin-mediated DNA damage. Scientific reports 33 29396485
2016 Sam68 Is Required for DNA Damage Responses via Regulating Poly(ADP-ribosyl)ation. PLoS biology 32 27635653
2004 Depolarization-induced translocation of the RNA-binding protein Sam68 to the dendrites of hippocampal neurons. Journal of cell science 32 14996936
2002 Functional interaction of Sam68 and heterogeneous nuclear ribonucleoprotein K. Oncogene 32 12370808
2016 Sam68 functions as a transcriptional coactivator of the p53 tumor suppressor. Nucleic acids research 31 27365047
2015 Sam68 Promotes NF-κB Activation and Apoptosis Signaling in Articular Chondrocytes during Osteoarthritis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 30 26350037
2020 Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer. International journal of molecular sciences 29 32033341
2015 Analysis of the interaction between host factor Sam68 and viral elements during foot-and-mouth disease virus infections. Virology journal 29 26695943
2007 The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G. Biochimica et biophysica acta 29 17890166
2018 Sam68 Promotes Invasion, Migration, and Proliferation of Fibroblast-like Synoviocytes by Enhancing the NF-κB/P65 Pathway in Rheumatoid Arthritis. Inflammation 28 29785588
2017 Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing. Human reproduction (Oxford, England) 28 28938739
2015 Sam68 Regulates S6K1 Alternative Splicing during Adipogenesis. Molecular and cellular biology 28 25776557
2021 Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified. Nature communications 27 34140493
2021 SAM68 promotes tumorigenesis in lung adenocarcinoma by regulating metabolic conversion via PKM alternative splicing. Theranostics 26 33537092
2020 Sam68 promotes aerobic glycolysis in colorectal cancer by regulating PKM2 alternative splicing. Annals of translational medicine 25 32395503
2013 The nuclear protein Sam68 is redistributed to the cytoplasm and is involved in PI3K/Akt activation during EV71 infection. Virus research 25 24316008
2009 Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1. Experimental cell research 25 19615357
2019 SAM68 interaction with U1A modulates U1 snRNP recruitment and regulates mTor pre-mRNA splicing. Nucleic acids research 24 30767021
2011 Met receptors induce Sam68-dependent cell migration by activation of alternate extracellular signal-regulated kinase family members. The Journal of biological chemistry 24 21489997
2009 Identification of a Sam68 ribonucleoprotein complex regulated by epidermal growth factor. The Journal of biological chemistry 24 19762470
1999 Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src. Oncogene 24 10467411
2021 Sam68 promotes hepatic gluconeogenesis via CRTC2. Nature communications 23 34099657
2009 Sam68: a new STAR in the male fertility firmament. Journal of andrology 23 19875495
2004 Somatodendritic localization and mRNA association of the splicing regulatory protein Sam68 in the hippocampus and cortex. Journal of neuroscience research 23 14991841
1998 Sam68 is a Ras-GAP-associated protein in mitosis. Biochemical and biophysical research communications 23 9571195
2022 Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51. Oncogene 22 35217791
2015 MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68. Molecular medicine reports 22 26136151
2007 Targeting the RNA-binding protein Sam68 as a treatment for cancer? Future oncology (London, England) 22 17927519
2001 Identification of Sam68 arginine glycine-rich sequences capable of conferring nonspecific RNA binding to the GSG domain. The Journal of biological chemistry 21 11395494
2020 KMT Set7/9 is a new regulator of Sam68 STAR-protein. Biochemical and biophysical research communications 20 32178870
2019 A comprehensive study on genome-wide coexpression network of KHDRBS1/Sam68 reveals its cancer and patient-specific association. Scientific reports 20 31366900
2018 Novel KHDRBS1-NTRK3 rearrangement in a congenital pediatric CD34-positive skin tumor: a case report. Virchows Archiv : an international journal of pathology 20 30187166
2016 Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush. Biochemical and biophysical research communications 20 27059137
2016 Sam68 modulates apoptosis of intestinal epithelial cells via mediating NF-κB activation in ulcerative colitis. Molecular immunology 20 27235792

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