Affinage

SRF

Serum response factor · UniProt P11831

Length
508 aa
Mass
51.6 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRF is a MADS-box transcription factor that binds CArG box (CC(A/T)₆GG) DNA elements as a homodimer and serves as a central integrator of cytoskeletal, mitogenic, and differentiation signals by engaging two competing cofactor families: MRTF/myocardin-related factors, activated by Rho/Rac-dependent actin polymerization and nuclear G-actin depletion, and TCF/Elk-1 ternary complex factors, activated by MAP kinase/ERK signaling (PMID:1748287, PMID:8103935, PMID:27867007). TCFs and MRTFs compete directly for SRF binding, with TCF-dominated programs driving immediate-early gene expression and proliferation while MRTF-dominated programs control contractile, cytoskeletal, and smooth/cardiac/skeletal muscle gene expression; upstream regulators including GSK-3 phosphorylation of SRF, MICAL-2-mediated nuclear actin oxidation, filamin A scaffolding, and HDAC6 deacetylation of MRTF-A modulate cofactor selectivity and nuclear availability (PMID:24623780, PMID:24440334, PMID:26554816, PMID:30623138). Conditional knockout studies across tissues demonstrate essential roles for SRF in cortical actin assembly and mitotic cell rounding in epidermis, satellite cell fusion in skeletal muscle, tip cell filopodia and blood-brain barrier integrity in endothelium, pericyte migration and vascular tone, cardiomyocyte maturation, and neuronal mitochondrial dynamics (PMID:21336301, PMID:29269426, PMID:23674601, PMID:26221020, PMID:35862101, PMID:33361330, PMID:22927399). SRF activity is further shaped by feedback loops—FHL2 competes with MRTFs for SRF binding while being itself an SRF/MRTF target, and Elk-1 drives SRF promoter transcription—and by cross-talk with YAP-TEAD and Hedgehog/GLI1 signaling pathways (PMID:15610731, PMID:15531578, PMID:29317486, PMID:29400712).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 High

    Identifying SRF as a CArG-box-binding MADS-box transcription factor that dimerizes for DNA recognition established the foundational mechanism by which growth factor-inducible and muscle-specific promoters are activated.

    Evidence EMSA, cDNA cloning, and reporter assays defining SRF DNA-binding specificity and dimerization

    PMID:1748287

    Open questions at the time
    • Crystal structure of SRF-DNA complex not yet solved in this study
    • No cofactors or upstream signals identified at this stage
  2. 1993 High

    Discovery that SRF forms a ternary complex with ETS-domain proteins SAP-1/Elk-1 at the SRE linked MAP kinase signaling to SRF-dependent transcription, defining the first cofactor axis for signal-regulated gene activation.

    Evidence Yeast genetic screen, co-immunoprecipitation, and in vitro binding assays

    PMID:8103935

    Open questions at the time
    • MRTF cofactor family not yet discovered
    • In vivo relevance of ternary complex not tested by genetic loss-of-function
  3. 2002 Medium

    Identification of a dominant-negative SRF splice variant (SRF-Δ4,5) in failing human hearts raised the possibility that SRF activity is regulated post-transcriptionally in disease, though this was demonstrated only in overexpression systems.

    Evidence RT-PCR from failing heart tissue, reporter assays with overexpressed splice variant

    PMID:11893590

    Open questions at the time
    • Endogenous stoichiometry and functional impact in vivo not determined
    • No loss-of-function validation of the splice isoform
  4. 2004 High

    Discovery of opposing feedback loops—FHL2 competing with MRTF for SRF binding, and Elk-1 driving SRF gene expression—revealed that SRF cofactor balance is dynamically regulated and self-tuning.

    Evidence ChIP, reciprocal Co-IP, and functional reporter assays for FHL2 competition; ChIP and reporter assays for Elk-1-driven SRF promoter activation

    PMID:15531578 PMID:15610731

    Open questions at the time
    • Quantitative modeling of feedback dynamics absent
    • In vivo relevance of Elk-1-SRF autoregulation not tested by genetic approaches
  5. 2008 High

    Demonstrating that epithelial junction disruption activates SRF through Rac1 (not RhoA) and MRTF/G-actin revealed that the Rho-family GTPase identity coupling actin to SRF is cell-type-dependent.

    Evidence Clostridial toxin-based Rac/Rho inhibition, siRNA, and reporter assays in epithelial cells

    PMID:18334560

    Open questions at the time
    • Precise Rac1 effector linking to G-actin depletion not identified
    • Generalizability across epithelial subtypes not tested
  6. 2009 High

    Establishing that MRTF-SRF transcriptional targets MYH9 and MYL9 are required for tumor cell invasion and experimental metastasis connected SRF-driven cytoskeletal gene programs to cancer cell motility.

    Evidence RNAi, xenograft lung metastasis assays, invasion assays, and gene expression profiling

    PMID:19198601

    Open questions at the time
    • Whether SRF loss suppresses metastasis in autochthonous cancer models unknown
    • Relative contribution of individual SRF target genes not dissected
  7. 2011 High

    Conditional SRF deletion in epidermis revealed that SRF transcriptionally controls cortical actin regulators needed for mitotic rounding and proper spindle orientation, linking a transcription factor to cell division mechanics.

    Evidence Epidermal-specific Srf conditional KO mice, live imaging, FRAP, shRNA and actin inhibitor rescue

    PMID:21336301

    Open questions at the time
    • Which specific actin regulators are the essential SRF targets for rounding not fully resolved
    • Relevance to non-epidermal epithelia not tested
  8. 2012 High

    SRF deletion in neurons caused mitochondrial fragmentation and impaired ATP metabolism, rescued by constitutively active SRF-VP16, establishing that the SRF–cofilin–actin axis regulates neuronal mitochondrial dynamics beyond its canonical transcriptional role in cytoskeletal genes.

    Evidence Srf conditional KO neurons, SRF-VP16 rescue, live imaging, ATP assays, cofilin/slingshot epistasis

    PMID:22927399

    Open questions at the time
    • Direct SRF target genes mediating mitochondrial phenotype not identified
    • Whether this is MRTF-dependent or TCF-dependent not resolved
  9. 2013 High

    Endothelial-specific Srf deletion demonstrated that SRF is required for tip cell filopodia formation and VEGF-A-induced MRTF nuclear accumulation during sprouting angiogenesis, extending SRF's role to vascular morphogenesis.

    Evidence Inducible endothelial Srf KO mice, in vitro migration assays, nuclear localization imaging

    PMID:23674601

    Open questions at the time
    • Whether tip cell versus stalk cell programs require distinct SRF cofactor combinations unknown
    • Interaction with Notch lateral inhibition pathway not explored
  10. 2014 High

    Two discoveries resolved key upstream regulatory mechanisms: MICAL-2 was shown to activate MRTF-A/SRF by redox-depolymerizing nuclear actin, and GSK-3 was found to phosphorylate SRF to selectively promote MKL but not TCF cofactor interaction.

    Evidence In vitro actin depolymerization plus nuclear fractionation for MICAL-2; in vitro kinase assay plus mutagenesis plus Co-IP for GSK-3

    PMID:24440334 PMID:24623780

    Open questions at the time
    • Nuclear actin pool size and dynamics remain technically difficult to quantify
    • GSK-3 phosphorylation site conservation across species and tissues not fully characterized
  11. 2015 High

    Multiple 2015 studies expanded SRF's tissue roles: endothelial SRF/MRTF controls blood-brain barrier integrity through tight/adherens junction genes; filamin A scaffolds MKL1 to transduce actin polymerization to SRF; SRF cooperates with MEF2 to drive skeletal muscle LMOD3 expression; and YAP physically binds SRF at mammary stem cell gene promoters.

    Evidence Endothelial Srf conditional KO with MRI/expression analysis; FLNA-MKL1 reciprocal Co-IP with migration assays; Lmod3/Klhl40 circuit via conditional KO plus ChIP; YAP-SRF Co-IP plus ChIP

    PMID:25774500 PMID:26221020 PMID:26554816 PMID:26671411

    Open questions at the time
    • Whether FLNA-MKL1 interaction is direct or bridged by F-actin not fully resolved
    • YAP-SRF interaction confirmed in one lab only
    • Relative contribution of SRF versus Smad/Notch to BBB maintenance unclear
  12. 2016 High

    Genome-wide analysis in TCF triple-KO cells established that TCFs and MRTFs compete directly for SRF across the genome, with TCF inactivation causing unopposed MRTF-SRF activity and hypercontractility—quantifying the cofactor competition model.

    Evidence ChIP-seq, RNA-seq, Hi-C in TCF triple-KO MEFs

    PMID:27867007

    Open questions at the time
    • Whether cofactor competition operates identically in differentiated muscle cells unknown
    • 3D genome reorganization upon cofactor loss not deeply explored
  13. 2017 High

    Satellite cell-specific Srf KO revealed SRF controls myoblast fusion specifically (not proliferation or differentiation) by maintaining actin-based protrusions at fusion sites, rescued by α-actin overexpression.

    Evidence Satellite cell conditional KO, live imaging, α-actin rescue of fusion

    PMID:29269426

    Open questions at the time
    • Fusogenic receptors regulated by SRF not identified
    • Whether this fusion role extends to other cell types (macrophages, trophoblasts) unknown
  14. 2018 High

    Several advances refined SRF's signaling integration: single-molecule imaging showed SRF chromatin residence time increases upon MRTF activation; MRTF-SRF and YAP-TEAD were shown to be mutually dependent through indirect cytoskeletal cross-talk; and SRF-MKL1-GLI1 complex formation was identified as a noncanonical Hedgehog activation mechanism.

    Evidence Single-molecule Halo-tag imaging with pharmacological perturbation; ChIP-seq/RNA-seq epistasis in fibroblasts; Co-IP plus MKL inhibitor in BCCs

    PMID:29317486 PMID:29400712 PMID:30598445

    Open questions at the time
    • Structural basis of SRF chromatin residence time modulation unknown
    • Whether SRF-GLI1 interaction is direct or MKL1-bridged not resolved
    • YAP-MRTF cross-talk stoichiometry in physiological contexts unclear
  15. 2019 Medium

    Additional upstream regulators were mapped: TRPM7 channel/kinase activity controls MRTF-A/SRF via RhoA phosphorylation and FLNA; HDAC6 deacetylates MRTF-A to modulate nuclear translocation; and IGF2BP1 stabilizes SRF mRNA in an m6A-dependent manner.

    Evidence TRPM7 pharmacological/CRISPR KO with nuclear fractionation; HDAC6 Co-IP plus inhibitor plus in vivo artery injury; RIP/m6A-IP/RNA stability assays

    PMID:30371874 PMID:30623138 PMID:31844251

    Open questions at the time
    • HDAC6-MRTF-A deacetylation site(s) not mapped
    • Whether IGF2BP1-mediated SRF mRNA stabilization operates in normal physiology versus cancer unknown
    • TRPM7-RhoA phosphorylation mechanism not reconstituted in vitro
  16. 2021 High

    Demonstrating that sarcomere disorganization (Actn2 mutation) sequesters MRTF-A via cytoplasmic monomeric actin binding established how structural feedback from the contractile apparatus regulates SRF transcriptional output in cardiomyocytes.

    Evidence Conditional Actn2 KO mice, nuclear fractionation, Co-IP of actin-MRTF-A, dominant-negative MRTF-A phenocopy

    PMID:33361330

    Open questions at the time
    • Whether actin isoform specificity determines MRTF sequestration efficiency unknown
    • Human cardiomyopathy correlation not established
  17. 2022 High

    Three discoveries extended SRF function to new physiological contexts: in LMNA-mutant cardiomyopathy, ERK-phosphorylated cofilin-1 sequesters MRTF-A leading to reduced SRF-dependent ATAT1 and Connexin 43 mislocalization; in mural cells, PDGFB/PDGFRB activates SRF via MRTFs to control vascular tone; and MRTF-SRF was identified as a direct transcriptional regulator of circadian clock genes Per2, Nr1d1, and Nfil3.

    Evidence Co-IP plus LMNA-mutant patient cardiomyocytes plus pharmacological rescue; mural cell Srf conditional KO plus live imaging; ChIP plus genetic KO plus circadian reporters

    PMID:35862101 PMID:36093830 PMID:36550158

    Open questions at the time
    • Whether SRF-dependent circadian regulation operates in non-fibroblast tissues not tested
    • Direct PDGFRB-to-MRTF signaling intermediates not fully mapped
    • Therapeutic targeting of cofilin-MRTF axis in laminopathies not validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for cofactor competition at SRF, the relative contribution of individual SRF target genes to tissue-specific phenotypes, whether SRF chromatin dynamics differ between MRTF- and TCF-dependent gene classes in vivo, and the therapeutic potential of selectively modulating SRF cofactor interactions in disease.
  • No high-resolution structure of SRF bound simultaneously with MRTF versus TCF
  • Systematic in vivo identification of essential SRF target genes per tissue lacking
  • Cofactor-selective SRF modulators not yet developed for clinical use

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 3 R-HSA-397014 Muscle contraction 3 R-HSA-9909396 Circadian clock 1
Partners
ELK1FHL2FOXK1GLI1KAT8MKL1MRTFAYAP1
Complex memberships
SRF-MKL1-GLI1 complexSRF-MRTF complexSRF-TCF/Elk-1 ternary complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 SRF is a transcription factor that binds the CC(A/T)6GG (CArG box) sequence found in growth factor-inducible and muscle-specific promoters; SRF-related proteins (RSRFs) contain an 86-amino-acid DNA-binding domain homologous to SRF but recognize the distinct consensus CTA(A/T)4TAG, bind DNA as dimers, and can dimerize with each other but not with SRF. DNA binding assays, gel-shift/EMSA, cDNA cloning, transfection reporter assays Genes & development High 1748287
1993 SRF forms a ternary complex with p62/TCF (SAP-1/Elk-1) at the serum response element (SRE); SAP-1 and Elk-1 contain conserved regions for cooperative interaction with SRF and MAP kinase phosphorylation sites, linking growth factor signaling to SRF-dependent transcription. Yeast genetic screen, co-immunoprecipitation, in vitro binding assays Philosophical transactions of the Royal Society of London. Series B, Biological sciences High 8103935
2004 SRF directly binds the Fhl2 promoter in vivo and drives Fhl2 expression in response to RhoA activation; FHL2 protein physically interacts with SRF and competes with the coactivator MAL/MRTF-A for SRF binding, selectively antagonizing induction of smooth muscle (SM) gene targets but not immediate-early genes or cardiac genes, establishing an autoregulatory feedback loop. ChIP, co-immunoprecipitation, expression profiling, reporter assays Molecular cell High 15610731
2004 The ETS-domain TCF Elk-1 binds the SRF gene promoter in a ternary complex with SRF and activates SRF expression, establishing a positive feedback loop whereby TCF activation enhances its own partner protein SRF. ChIP, reporter assays, EMSA, RNA and protein expression analysis The Journal of biological chemistry Medium 15531578
2007 SRF physically interacts with the Forkhead transcription factor FOXK1; FOXK1 binding to SM alpha-actin and PPGB promoters requires SRF occupancy on the promoter, and FOXK1 acts as a transcriptional repressor of these SRF target genes. Co-immunoprecipitation, ChIP, reporter assays Nucleic acids research Medium 17670796
2008 Ca2+-dependent dissociation of epithelial junctions activates SRF-mediated transcription through a Rac1–G-actin–MAL/MRTF pathway; Rac (not RhoA) is specifically required for SRF activation in epithelial cells, and actomyosin contractility is required but not sufficient. Clostridial cytotoxins (Rac/Rho inhibitors), siRNA knockdown, reporter assays, EMSA Journal of cell science High 18334560
2009 MRTF-SRF signaling is required for cytoskeletal dynamics including cell adhesion, spreading, invasion, and motility in tumor cells; MRTF-SRF targets MYH9 (NMHCIIa) and MYL9 (MLC2), which are required for invasion and experimental lung metastasis. RNAi depletion, xenograft assays, in vitro invasion/motility assays, gene expression profiling Nature cell biology High 19198601
2011 Conditional Srf deletion in epidermis reveals that SRF transcriptionally controls actin regulators required for cortical actomyosin network assembly; without SRF, cells fail to round up during mitosis, leading to defective spindle orientation, asymmetric cell division, and impaired epidermal stratification. Conditional knockout, live imaging, shRNA knockdown, actin inhibitor treatments, FRAP Nature cell biology High 21336301
2012 SRF deficiency in neurons causes mitochondrial fragmentation, impaired motility, and disrupted ATP metabolism; constitutively active SRF-VP16 rescues huntingtin-impaired mitochondrial dynamics. The SRF–cofilin–actin signaling axis modulates neuronal mitochondrial function. SRF conditional KO neurons, SRF-VP16 overexpression, live imaging, ATP assays, genetic epistasis with cofilin/slingshot phosphatase Proceedings of the National Academy of Sciences of the United States of America High 22927399
2013 Endothelial SRF is selectively required for tip cell filopodia formation and contractility during sprouting angiogenesis; VEGF-A induces nuclear accumulation of MRTFs and regulates MRTF/SRF-dependent Myl9 expression, which is necessary for endothelial cell migration. Inducible endothelial-specific Srf KO mice, in vitro migration assays, nuclear localization imaging Development (Cambridge, England) High 23674601
2014 MICAL-2 induces redox-dependent depolymerization of nuclear actin, decreasing nuclear G-actin levels and increasing nuclear MRTF-A, thereby activating SRF/MRTF-A-dependent gene transcription; MICAL-2 is also the target of the SRF/MRTF-A inhibitor CCG-1423. In vitro actin depolymerization assays, nuclear fractionation, reporter assays, pharmacological inhibition Cell High 24440334
2014 GSK-3 directly phosphorylates SRF on a conserved serine residue; this phosphorylation is necessary for SRF transcriptional activity and for SRF interaction with MKL-family cofactors (MKL1/MKL2) but not TCF-family cofactor Elk-1, and promotes axon outgrowth in hippocampal neurons. In vitro kinase assay, co-immunoprecipitation, site-directed mutagenesis, shRNA knockdown, rescue experiments The Journal of neuroscience High 24623780
2015 SRF cooperates with MEF2 to drive transcription of Lmod3 (leiomodin-3) in skeletal muscle; LMOD3 and its stabilizing partner KLHL40 in turn enhance MRTF-SRF transcriptional activity, establishing a positive regulatory circuit that maintains skeletal muscle contractile apparatus. Conditional KO mice, ChIP, reporter assays, genetic epistasis The Journal of clinical investigation High 25774500
2015 Filamin A (FLNA) physically interacts with the SRF coactivator MKL1; F-actin–bound FLNA promotes MKL1 nuclear localization and SRF-dependent target gene expression. LPA-induced RhoA activation enhances MKL1-FLNA association, while actin polymerization inhibitors dissociate it, demonstrating FLNA as a positive transducer linking actin polymerization to MKL1-SRF activity. Co-immunoprecipitation, domain mapping, cell migration assays, MKL1 interaction-deficient mutants Science signaling High 26554816
2015 Endothelial-specific depletion of SRF or its cofactors MRTF-A/B causes loss of blood-brain barrier integrity and intracerebral hemorrhage; SRF/MRTF directly regulate structural components of tight junctions (Claudins, ZO proteins), adherens junctions (VE-cadherin, α-Actinin), and basement membrane (Collagen IV). Conditional endothelial-specific KO, MRI imaging, gene expression analysis, in vivo vascular integrity assays Proceedings of the National Academy of Sciences of the United States of America High 26221020
2015 YAP physically binds SRF and is recruited by SRF to mammary stem cell signature gene promoters to induce gene expression including IL-6, which mediates YAP-induced stemness in mammary epithelial cells and basal-like breast cancer. Co-immunoprecipitation, ChIP, reporter assays, functional stemness assays Nature communications Medium 26671411
2016 TCFs (ternary complex factors) and MRTFs compete directly for binding to SRF; TCFs act as general antagonists of MRTF-dependent SRF target gene expression. TCF inactivation inhibits over 60% of TPA-inducible gene transcription and impairs proliferation, while TCF-deficient cells exhibit hypercontractile behavior due to unopposed MRTF-SRF activity. ChIP-seq, Hi-C, TCF triple-KO MEFs, RNA-seq, reporter assays Molecular cell High 27867007
2017 SRF controls satellite cell fusion (not proliferation or differentiation) by maintaining an actin cytoskeleton network; Srf deletion abolishes actin-based finger-like protrusions at fusion sites, and this defect is rescued by overexpression of α-actin, restoring polymerized actin and fusion. Satellite cell-specific conditional KO, in vitro fusion assays, rescue with actin overexpression, live imaging The Journal of cell biology High 29269426
2018 SRF forms a protein complex with its coactivator MKL1 (MRTF-A) and the hedgehog transcription factor GLI1, amplifying GLI1 transcriptional activity in a noncanonical hedgehog activation pathway; cytoskeletal activation through Rho and the formin mDia is required for this SRF-MKL-GLI1 axis. Co-immunoprecipitation, genomic analysis of drug-resistant BCCs, functional cell viability assays, MKL inhibitor studies Nature medicine Medium 29400712
2018 MRTF-SRF and YAP-TEAD pathways exhibit mutual dependence in cancer-associated fibroblasts; cross-talk is indirect, mediated through their target genes: MRTF-SRF-driven contractility activates YAP, while YAP-TEAD-dependent TGFβ signaling activates MRTF-SRF. Each pathway requires recruitment to DNA via its own DNA-binding partner (SRF or TEAD). ChIP-seq, RNA-seq, dominant-negative and constitutively active constructs, siRNA knockdown, epistasis experiments Genes & development High 29317486
2018 Single-molecule imaging reveals SRF binds chromatin with short, intermediate, and long residence times; upon stimulation, the long-bound fraction increases and correlates with activation of MRTF-A and MRTF-B cofactors. SRF chromatin occupancy is modulated by actin signaling, MAP kinases, and MRTFs. Single-molecule live-cell imaging of Halo-tagged SRF, pharmacological pathway perturbations Proceedings of the National Academy of Sciences of the United States of America High 30598445
2018 HDAC6 physically interacts with and deacetylates MRTF-A; HDAC6 inhibition increases MRTF-A acetylation and protein levels and enhances MRTF-A nuclear translocation to activate SRF-dependent transcription, thereby maintaining vascular smooth muscle contractile gene expression. Co-immunoprecipitation, HDAC6 inhibition (tubastatin A), siRNA knockdown, luciferase reporter assays, in vivo carotid artery injury model JACC. Basic to translational science Medium 30623138
2019 SRF promotes ROS generation and hepatic stellate cell activation by recruiting the histone acetyltransferase KAT8 to the NCF1 and NCF2 promoters, epigenetically activating their transcription; SRF-conditional KO mice show reduced liver fibrosis and attenuated ROS levels. Conditional KO mice, ChIP, Co-immunoprecipitation, ROS assays, gene expression analysis Redox biology High 31442911
2019 IGF2BP1 promotes SRF expression in an m6A- and miRNA-dependent manner by impairing miRNA-directed decay of SRF mRNA; elevated SRF in turn increases SRF-dependent transcriptional activity and promotes tumor cell growth and invasion. RIP, m6A-IP, reporter assays, RNA stability assays, siRNA knockdown Nucleic acids research Medium 30371874
2019 TRPM7 channel-mediated Mg2+ influx and TRPM7 kinase-mediated phosphorylation of RhoA regulates actin polymerization, MRTF-A–Filamin A complex formation, and MRTF-A/SRF target gene expression; TRPM7 blockade displaces MRTF-A from the nucleus and suppresses SRF-dependent transcription. Pharmacological TRPM7 inhibition, CRISPR genome editing, nuclear fractionation, reporter assays, xenograft models Oncogene Medium 31844251
2020 Exercise-induced phosphorylation of MRTF-B is required for its nuclear translocation and subsequent SRF target gene (Fos) induction; MSK1/2 kinases phosphorylate histone H3 on serine 10 at SRF target gene loci after high-intensity exercise, and MSK1/2 ablation prevents both histone modification and increases in protein synthesis. Phosphoproteomics, in vivo electrical stimulation, MSK1/2 KO mice, ChIP, human biopsy analysis Acta physiologica Medium 32408395
2021 Sarcomere organization via α-actinin-2 (Actn2) regulates cardiomyocyte maturation through MRTF-SRF signaling; Actn2 mutation increases monomeric cardiac α-actin, which binds MRTF-A in the cytoplasm and prevents SRF nuclear activation. Overexpression of dominant-negative MRTF-A recapitulates Actn2/Srf mutant morphological and transcriptional defects. Conditional KO mice, nuclear fractionation, Co-immunoprecipitation, dominant-negative constructs, transcriptomic analysis Proceedings of the National Academy of Sciences of the United States of America High 33361330
2022 In LMNA-mutant cardiomyopathy, ERK1/2-phosphorylated cofilin-1 (phospho-T25) binds MRTF-A in the cytoplasm, preventing SRF nuclear activation; reduced MRTF-A/SRF activity decreases ATAT1 expression, leading to reduced α-tubulin acetylation and mislocalization of Connexin 43. Co-immunoprecipitation, conditional KO mice (Atat1 KO), patient-derived cardiomyocytes, tubastatin A rescue treatment, immunofluorescence Nature communications High 36550158
2022 In mural cells, PDGFB/PDGFRB signaling activates SRF via MRTF cofactors to promote pericyte migration during retinal angiogenesis; SRF regulates contractile SMC protein expression required for vascular tone, and its loss causes arteriovenous shunt formation. Inducible mural cell-specific Srf KO mice, RNA-seq, immunohistology, in vivo live imaging, in vitro assays Circulation research High 35862101
2022 The actin cytoskeleton-MRTF-A/SRF signaling cascade transduces extracellular matrix physical cues to modulate circadian clock period and amplitude; Per2, Nr1d1, and Nfil3 are identified as direct MRTF-A/SRF transcriptional targets mediating actin dynamics-induced clock responses. Integrin/FAK signaling upstream regulates MRTF-SRF activity. Pharmacological inhibitors (ROCK, actin drugs, FAK inhibitor), Srf and Mrtfa genetic KO, ChIP, circadian reporter assays Journal of cell science Medium 36093830
2002 An alternatively spliced SRF isoform (SRF-Δ4,5, ~52 kDa) lacking exons 4 and 5 is expressed in failing human hearts and functions as a dominant-negative inhibitor of SRF-dependent cardiac muscle gene activation. RT-PCR, Southern blot, Western blot, cDNA cloning, overexpression reporter assays American journal of physiology. Heart and circulatory physiology Medium 11893590
2010 SRF directly regulates expression of FXN (frataxin) by binding to CArG-box sequences in the FXN promoter; mutagenesis of SRF binding sites reduces FXN promoter activity, and SRF overexpression increases frataxin mRNA and protein levels. ChIP, EMSA, mutagenesis, luciferase reporter assays, overexpression in cell lines and patient lymphoblasts PloS one Medium 20808827

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes & development 384 1748287
2009 Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis. Nature cell biology 353 19198601
2019 IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner. Nucleic acids research 303 30371874
1998 Crystal structure of the yeast MATalpha2/MCM1/DNA ternary complex. Nature 193 9490409
2014 Novel Rho/MRTF/SRF inhibitors block matrix-stiffness and TGF-β-induced fibrogenesis in human colonic myofibroblasts. Inflammatory bowel diseases 170 24280883
1997 A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription. Genes & development 168 9171372
2018 Mutual dependence of the MRTF-SRF and YAP-TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics. Genes & development 164 29317486
1992 A molecular mechanism for combinatorial control in yeast: MCM1 protein sets the spacing and orientation of the homeodomains of an alpha 2 dimer. Cell 155 1732062
2015 A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. Nature communications 149 26671411
2014 Redox modification of nuclear actin by MICAL-2 regulates SRF signaling. Cell 139 24440334
2011 Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation. Nature cell biology 137 21336301
2002 Conserved homeodomain proteins interact with MADS box protein Mcm1 to restrict ECB-dependent transcription to the M/G1 phase of the cell cycle. Genes & development 137 12464633
2004 The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF. Molecular cell 136 15610731
2016 SRF Co-factors Control the Balance between Cell Proliferation and Contractility. Molecular cell 134 27867007
2009 Functional versatility of transcription factors in the nervous system: the SRF paradigm. Trends in neurosciences 123 19643506
2012 The actin-MRTF-SRF gene regulatory axis and myofibroblast differentiation. Journal of cardiovascular translational research 122 22898751
1991 A new role for MCM1 in yeast: cell cycle regulation of SW15 transcription. Genes & development 110 1752436
1996 Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1. Molecular and cellular biology 99 8649392
1992 The SRF and MCM1 transcription factors. Current opinion in genetics & development 98 1638115
2014 SRF expedites metastasis and modulates the epithelial to mesenchymal transition by regulating miR-199a-5p expression in human gastric cancer. Cell death and differentiation 88 25080937
1991 Functional domains of the yeast transcription/replication factor MCM1. Genes & development 88 1851120
2018 Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas. Nature medicine 87 29400712
2017 MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer. Theranostics 85 28900514
1992 Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis. The EMBO journal 85 1281451
2008 Epithelial cell-cell contacts regulate SRF-mediated transcription via Rac-actin-MAL signalling. Journal of cell science 81 18334560
2018 SRF'ing and SAP'ing - the role of MRTF proteins in cell migration. Journal of cell science 79 30309957
2000 Srf(-/-) ES cells display non-cell-autonomous impairment in mesodermal differentiation. The EMBO journal 76 11060034
1996 SRF and TEF-1 control of chicken skeletal alpha-actin gene during slow-muscle hypertrophy. The American journal of physiology 76 8764144
2021 Sarcomeres regulate murine cardiomyocyte maturation through MRTF-SRF signaling. Proceedings of the National Academy of Sciences of the United States of America 67 33361330
2018 Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation. Proceedings of the National Academy of Sciences of the United States of America 66 30598445
2003 Arabidopsis inositol polyphosphate 6-/3-kinase is a nuclear protein that complements a yeast mutant lacking a functional ArgR-Mcm1 transcription complex. The Plant cell 66 12566584
1991 The DNA binding and oligomerization domain of MCM1 is sufficient for its interaction with other regulatory proteins. The EMBO journal 65 1756728
2019 Serum response factor (SRF) promotes ROS generation and hepatic stellate cell activation by epigenetically stimulating NCF1/2 transcription. Redox biology 63 31442911
2002 Increased expression of alternatively spliced dominant-negative isoform of SRF in human failing hearts. American journal of physiology. Heart and circulatory physiology 58 11893590
2013 SRF selectively controls tip cell invasive behavior in angiogenesis. Development (Cambridge, England) 57 23674601
1998 Altered srf expression in Bacillus subtilis resulting from changes in culture pH is dependent on the Spo0K oligopeptide permease and the ComQX system of extracellular control. Journal of bacteriology 57 9515911
2017 Srf controls satellite cell fusion through the maintenance of actin architecture. The Journal of cell biology 56 29269426
1991 Both activation and repression of a-mating-type-specific genes in yeast require transcription factor Mcm1. Proceedings of the National Academy of Sciences of the United States of America 55 1961765
2017 SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model. Molecular brain 50 28716058
2000 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 by the pleiotropic factor ArgRIII is required for their stability. Molecular microbiology 49 10632874
1997 Multiple phosphorylated forms of the Saccharomyces cerevisiae Mcm1 protein include an isoform induced in response to high salt concentrations. Molecular and cellular biology 49 9001236
2006 A STE12 homologue of the homothallic ascomycete Sordaria macrospora interacts with the MADS box protein MCM1 and is required for ascosporogenesis. Molecular microbiology 48 16999832
2002 Interactions of the Mcm1 MADS box protein with cofactors that regulate mating in yeast. Molecular and cellular biology 48 12052870
2017 Rho Kinase Regulates Aortic Vascular Smooth Muscle Cell Stiffness Via Actin/SRF/Myocardin in Hypertension. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 47 29169155
2022 Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations. Nature communications 46 36550158
1991 Relative contributions of MCM1 and STE12 to transcriptional activation of a- and alpha-specific genes from Saccharomyces cerevisiae. Molecular & general genetics : MGG 44 1905781
2015 Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3. The Journal of clinical investigation 43 25774500
2015 Endothelial depletion of murine SRF/MRTF provokes intracerebral hemorrhagic stroke. Proceedings of the National Academy of Sciences of the United States of America 43 26221020
2015 Filamin A interacts with the coactivator MKL1 to promote the activity of the transcription factor SRF and cell migration. Science signaling 43 26554816
2012 Serum Response Factor (SRF)-cofilin-actin signaling axis modulates mitochondrial dynamics. Proceedings of the National Academy of Sciences of the United States of America 43 22927399
2003 Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1. The Journal of biological chemistry 43 12738768
1994 MCM1 point mutants deficient in expression of alpha-specific genes: residues important for interaction with alpha 1. Molecular and cellular biology 43 8139556
2019 Inhibition of TRPM7 blocks MRTF/SRF-dependent transcriptional and tumorigenic activity. Oncogene 41 31844251
2000 ArgRII, a component of the ArgR-Mcm1 complex involved in the control of arginine metabolism in Saccharomyces cerevisiae, is the sensor of arginine. Molecular and cellular biology 41 10688655
2018 LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis. The Journal of investigative dermatology 40 30447238
1996 The yeast alpha2 and Mcm1 proteins interact through a region similar to a motif found in homeodomain proteins of higher eukaryotes. Molecular and cellular biology 40 8628280
2020 SRF-FOXO1 and SRF-NCOA1 Fusion Genes Delineate a Distinctive Subset of Well-differentiated Rhabdomyosarcoma. The American journal of surgical pathology 39 32187044
2012 MKLs: co-factors of serum response factor (SRF) in neuronal responses. The international journal of biochemistry & cell biology 39 22626970
2004 Regulation of Egr-1, SRF, and Sp1 mRNA expression in contracting skeletal muscle cells. Journal of applied physiology (Bethesda, Md. : 1985) 39 15310743
2018 UNC-120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans. Aging cell 38 29314608
2011 Differential requirement of the transcription factor Mcm1 for activation of the Candida albicans multidrug efflux pump MDR1 by its regulators Mrr1 and Cap1. Antimicrobial agents and chemotherapy 38 21343453
2020 Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling. Molecular therapy. Nucleic acids 36 32464548
2014 SRF phosphorylation by glycogen synthase kinase-3 promotes axon growth in hippocampal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 24623780
2006 Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology. Journal of neurochemistry 36 16945101
2022 Mural Cell SRF Controls Pericyte Migration, Vessel Patterning and Blood Flow. Circulation research 35 35862101
1993 SPT13 (GAL11) of Saccharomyces cerevisiae negatively regulates activity of the MCM1 transcription factor in Ty1 elements. Molecular and cellular biology 34 8380229
2020 Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling. Acta physiologica (Oxford, England) 33 32408395
2022 SRF: a seriously responsible factor in cardiac development and disease. Journal of biomedical science 32 35681202
2018 HDAC6 Regulates the MRTF-A/SRF Axis and Vascular Smooth Muscle Cell Plasticity. JACC. Basic to translational science 32 30623138
2017 Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4. Nature communications 32 28676626
2004 The ETS domain transcription factor Elk-1 regulates the expression of its partner protein, SRF. The Journal of biological chemistry 32 15531578
2014 MKL1/2 and ELK4 co-regulate distinct serum response factor (SRF) transcription programs in macrophages. BMC genomics 31 24758171
2014 The role of the MRTF-A/SRF pathway in ocular fibrosis. Investigative ophthalmology & visual science 30 25056592
2015 Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells. The EMBO journal 29 25896507
2010 Expression of human frataxin is regulated by transcription factors SRF and TFAP2. PloS one 29 20808827
2019 CBP and SRF co-regulate dendritic growth and synaptic maturation. Cell death and differentiation 28 30850733
1999 Identification of target sites of the alpha2-Mcm1 repressor complex in the yeast genome. Genome research 28 10568744
2007 Functional interactions between the Forkhead transcription factor FOXK1 and the MADS-box protein SRF. Nucleic acids research 26 17670796
2015 Dasatinib inhibits TGFβ-induced myofibroblast differentiation through Src-SRF Pathway. European journal of pharmacology 25 26548624
2010 The transcription factor Srf regulates hematopoietic stem cell adhesion. Blood 25 20709909
1993 Isolation and characterization of SRF accessory proteins. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 25 8103935
2018 Long noncoding RNA HOTTIP mediates SRF expression through sponging miR-150 in hepatic stellate cells. Journal of cellular and molecular medicine 24 30548190
2017 TGFβ-TAZ/SRF signalling regulates vascular smooth muscle cell differentiation. The FEBS journal 24 28342289
2009 Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas. Oncogene 24 19151755
2006 Effect of sequence-directed nucleosome disruption on cell-type-specific repression by alpha2/Mcm1 in the yeast genome. Eukaryotic cell 24 16980406
1997 The yeast homeodomain protein MATalpha2 shows extended DNA binding specificity in complex with Mcm1. The Journal of biological chemistry 24 9079665
2017 The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 28607167
2006 Cellular toxicity induced by SRF-mediated transcriptional squelching. Toxicological sciences : an official journal of the Society of Toxicology 23 17116645
2020 SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors. The American journal of surgical pathology 22 33021523
2022 The actin cytoskeleton-MRTF/SRF cascade transduces cellular physical niche cues to entrain the circadian clock. Journal of cell science 21 36093830
2018 RAC2 promotes abnormal proliferation of quiescent cells by enhanced JUNB expression via the MAL-SRF pathway. Cell cycle (Georgetown, Tex.) 21 29895215
2018 MRTFA augments megakaryocyte maturation by enhancing the SRF regulatory axis. Blood advances 21 30337297
2015 SRF-miR‑29b-MMP2 axis inhibits NSCLC invasion and metastasis. International journal of oncology 21 26044095
1992 The yeast alpha 1 and MCM1 proteins bind a single strand of their duplex DNA recognition site. Molecular and cellular biology 21 1630462
2017 miR-22 contributes to endosulfan-induced endothelial dysfunction by targeting SRF in HUVECs. Toxicology letters 20 28161397
2004 Alpha1-induced DNA bending is required for transcriptional activation by the Mcm1-alpha1 complex. Nucleic acids research 20 15118075
1995 The yeast Mcm1 protein is regulated posttranscriptionally by the flux of glycolysis. Molecular and cellular biology 20 7623855
2013 Bck2 acts through the MADS box protein Mcm1 to activate cell-cycle-regulated genes in budding yeast. PLoS genetics 19 23675312
1994 Genetic interactions between SIN3 mutations and the Saccharomyces cerevisiae transcriptional activators encoded by MCM1, STE12, and SWI1. Molecular & general genetics : MGG 19 7830715
2020 SRF-MRTF signaling suppresses brown adipocyte development by modulating TGF-β/BMP pathway. Molecular and cellular endocrinology 18 32603734