| 1998 |
STRAP (serine-threonine kinase receptor-associated protein) was identified as a novel WD40-domain protein that interacts with TGF-β type I receptor (TβR-I) in a yeast two-hybrid system and associates with both functional TβR-I and TβR-II in vivo. Overexpression of STRAP inhibits TGF-β-mediated transcriptional activation and shows synergistic inhibition with Smad7 but not Smad6. |
Yeast two-hybrid, co-immunoprecipitation, transcriptional reporter assays |
The Journal of biological chemistry |
High |
9856985
|
| 2000 |
STRAP synergizes specifically with Smad7 (not Smad6) to inhibit TGF-β-induced transcriptional responses by recruiting Smad7 to the activated type I receptor and stabilizing the Smad7-receptor complex, thereby preventing Smad2 and Smad3 access to the receptor. STRAP associates stably with Smad7 but not with a C-terminal deletion mutant of Smad7 that lacks receptor-binding activity. The C terminus of STRAP is required for its phosphorylation in vivo, which depends on TGF-β receptor kinases. |
Co-immunoprecipitation, transcriptional reporter assays, deletion mutagenesis, in vivo phosphorylation assay |
Molecular and cellular biology |
High |
10757800
|
| 2006 |
STRAP is localized in both cytoplasm and nucleus, and its stable expression activates the MEK/ERK pathway and downregulates the CDK inhibitor p21(Cip1), resulting in retinoblastoma protein hyperphosphorylation. STRAP-knockout mouse embryonic fibroblasts show enhanced Smad2/3 phosphorylation, TGF-β-mediated transcription, and growth inhibition compared to wild-type cells. |
Stable overexpression, knockdown by siRNA, western blotting, STRAP-knockout MEFs, subcellular fractionation/localization |
Cancer research |
High |
16778189
|
| 2007 |
NM23-H1 and STRAP directly interact with the central DNA-binding domain of p53 (residues 113–290). Specific cysteine residues mediate binding: Cys145 of NM23-H1 and Cys152/Cys270 of STRAP bind p53 at Cys176 and Cys135, respectively. NM23-H1 and STRAP potentiate p53 transcriptional activity and p53-induced apoptosis by removing Mdm2 from the p53-Mdm2 complex. |
Co-immunoprecipitation, mutagenesis, transcriptional reporter assays, apoptosis assays, siRNA knockdown |
The Journal of biological chemistry |
High |
17916563
|
| 2008 |
ATM kinase directly phosphorylates Strap, prompting its nuclear accumulation by impeding nuclear export. Subsequently, Chk2 kinase phosphorylates Strap to augment protein stability once Strap has attained a nuclear location. These two kinase-dependent events cooperate to regulate Strap during the DNA damage response. |
In vitro kinase assays, mutational analysis, nuclear/cytoplasmic fractionation, live-cell imaging |
EMBO reports |
High |
18833288
|
| 2008 |
p49/STRAP (SRFBP1) was identified as a cofactor of serum response factor (SRF) and interacts with NDUFAB1, a subunit of NADH dehydrogenase, via yeast two-hybrid. The two proteins co-localize in the cell. Overexpression of p49/STRAP alters intracellular NAD levels, reduces the NAD/NADH ratio, and induces deacetylation of SRF. |
Yeast two-hybrid, co-immunoprecipitation, co-localization, NAD/NADH measurement, SRF deacetylation assay |
BMC cell biology |
Medium |
18230186
|
| 2009 |
Deletion of STRAP from mouse embryonic fibroblasts (MEFs) results in loss of mesenchymal morphology and acquisition of epithelial features, upregulation of E-cadherin and formation of adherens junctions, β-catenin relocalization to the cell membrane, and downregulation of the mesenchymal marker LEF1. Upregulation of WT1 in STRAP-null MEFs drives E-cadherin induction. Stable re-expression of STRAP reverses this phenotype. |
STRAP-knockout MEFs, gene expression profiling, western blotting, immunofluorescence, stable re-expression |
Cellular signalling |
High |
19781628
|
| 2010 |
B-MYB is a STRAP-interacting protein; the N-terminal DNA-binding domain and a region (aa 373–468) of B-MYB mediate the interaction. B-MYB enhances STRAP-mediated inhibition of TGF-β signaling by modulating complex formation between the TGF-β receptor and SMAD3 or SMAD7, and stimulates STRAP-mediated p53-induced apoptosis and cell cycle arrest. B-MYB prevents Smad3 nuclear translocation and promotes p53 nuclear translocation. |
Co-immunoprecipitation, deletion mapping, transcriptional reporter assays, confocal microscopy, apoptosis assays |
The Journal of biological chemistry |
High |
21148321
|
| 2011 |
STRAP binds GSK3β through its WD40 domains, and STRAP, GSK3β, and Axin form a ternary complex. The intracellular fragment of Notch3 (ICN3) binds GSK3β through its ankyrin repeat domain and also binds STRAP through the ankyrin repeat region. STRAP reduces ubiquitination of ICN3, stabilizing it. Small-molecule GSK3β inhibitors reduce the STRAP-GSK3β interaction. |
Co-immunoprecipitation, deletion mapping, in vivo ubiquitination assay, small-molecule inhibitor treatment |
Cell cycle |
High |
21502811
|
| 2011 |
STRAP regulates c-Jun stability by decreasing its ubiquitylation and proteasomal degradation. Loss of STRAP in MEFs reduces phospho-c-Jun and total c-Jun, decreases cyclin D1 expression, and reduces cell growth. Overexpression of STRAP in STRAP-null fibroblasts restores c-Jun expression, and STRAP overexpression decreases ubiquitylation of c-Jun in 293T cells. |
STRAP-knockout MEFs, proteasome inhibition assay, ubiquitylation assay, stable re-expression, western blotting |
Biochemical and biophysical research communications |
High |
21397588
|
| 2012 |
Crystal structure of full-length Strap (stress-responsive activator of p300) was solved at 2.05 Å resolution, revealing an atypical six-tetratricopeptide repeat (TPR) protein that also contains an unexpected oligonucleotide/oligosaccharide-binding (OB)-fold domain. This domain organization provides an extended superhelical scaffold for protein-protein and protein-DNA interactions. Both TPR and OB-fold domains localize to chromatin of p53 target genes and exhibit intrinsic regulatory activity necessary for the Strap-dependent p53 response. |
X-ray crystallography, chromatin immunoprecipitation (ChIP), functional reporter assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
22362889
|
| 2013 |
STRAP is tethered to collagen α1(I) and α2(I) mRNAs via interaction with LARP6 (which directly binds the 5' stem-loop of collagen mRNAs) through LARP6's C-terminal domain. Tethered STRAP restrains translation of collagen α2(I) mRNA by interacting with eIF4A. In the absence of STRAP, collagen α2(I) mRNA is unrestrictedly loaded onto polysomes, causing imbalanced synthesis of α1(I) and α2(I) polypeptides, hypermodification of α1(I), and inefficient assembly of the collagen trimer. Supplementing STRAP partially restores these defects. |
RNA pulldown, polysome profiling, co-immunoprecipitation, siRNA knockdown, rescue experiment, collagen secretion assay |
Molecular and cellular biology |
High |
23918805
|
| 2014 |
MPK38 (murine protein serine/threonine kinase 38) directly phosphorylates STRAP at Ser188 via direct interaction. The STRAP-MPK38 complex is formed through Cys152 and Cys270 of STRAP and Cys339 and Cys377 of MPK38, suggesting redox-dependent interaction. MPK38-mediated Ser188 phosphorylation converts STRAP from an anti-apoptotic to a pro-apoptotic regulator, modulating ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways. |
In vitro kinase assay, mutagenesis, inducible shRNA knockdown, adenoviral delivery in mice, cell death assays |
Cell cycle |
High |
25485581
|
| 2014 |
Strap localizes to mitochondria where it interacts with ATP synthase. This interaction downregulates mitochondrial ATP production. Under glucose-limiting conditions, mitochondrial Strap sensitizes cancer cells to apoptosis. Strap also augments the apoptotic effects of mitochondrial p53. |
Subcellular fractionation, co-immunoprecipitation, ATP production assay, apoptosis assays, extracellular ATP rescue |
Cell death and differentiation |
High |
25168243
|
| 2014 |
STRAP downregulates E-cadherin and p21(Cip1) by abrogating the binding of transcription factor Sp1 to its consensus binding sites on these promoters. STRAP recruits HDAC1 to Sp1 binding sites in the p21(Cip1) promoter. Loss of STRAP stabilizes Sp1 by repressing its ubiquitination in G1 phase, leading to enhanced p21(Cip1) expression and cell cycle arrest. |
ChIP assay, STRAP-knockout MEFs, siRNA knockdown, luciferase reporter assay, ubiquitination assay, cell cycle analysis |
Cell cycle |
High |
25483064
|
| 2014 |
p49/STRAP overexpression reduces actin content in cultured cells, results in smaller cell size, and causes malformations in transgenic mice including asymmetric abdominal/thoracic cavities and cardiac morphology changes. p49/STRAP co-localizes with nucleolin in the nucleolus and has a BUD22 domain at its C-terminus. p49/STRAP alters expression of muscle-specific genes including the SRF gene. |
Transgenic mouse model, GFP co-localization, actin content measurement, gene expression analysis |
BMC cell biology |
Medium |
25183317
|
| 2016 |
STRAP binds GSK-3β and reduces phosphorylation, ubiquitylation, and degradation of β-catenin by preventing its binding to the destruction complex, thereby activating Wnt/β-catenin signaling and upregulating downstream targets including Cyclin D1, MMP2, MMP9, and β-TrCP. This promotes colorectal cancer invasion and metastasis. |
Co-immunoprecipitation, siRNA knockdown, western blotting, in vitro invasion assay, in vivo metastasis model, human CRC specimens |
Oncotarget |
High |
26910283
|
| 2016 |
STRAP acts as a scaffold protein in TLR2/4-mediated innate immune signaling by binding TAK1 and IKKα along with NF-κB subunit p65, enhancing TAK1-IKKα-p65 association, and facilitating p65 phosphorylation and nuclear translocation. STRAP depletion severely impairs IL-6, TNF-α, and IL-1β production in macrophages stimulated with TLR2 or TLR4 agonists. The C-terminal region of STRAP is essential for this activity. STRAP also translocates to the nucleus at later times after LPS stimulation to prolong IL-6 mRNA production. |
Co-immunoprecipitation, siRNA knockdown, overexpression, cytokine ELISA, nuclear translocation assay, C-terminus deletion |
Scientific reports |
High |
27934954
|
| 2017 |
STRAP acts as a scaffold protein in TLR3-triggered signaling by interacting with TBK1 and IRF3, enhancing IFN-β production. STRAP knockdown reduces both pro-inflammatory cytokine and IFN production in TLR3 agonist-stimulated macrophages. The C-terminus of STRAP is essential for its function in TLR3-mediated IL-6 and IFN-β production. |
Co-immunoprecipitation, siRNA knockdown, overexpression, cytokine ELISA, C-terminus deletion |
Cellular immunology |
High |
28651742
|
| 2017 |
STRAP antagonizes formation of the PRC2 chromatin modifier complex by competitively disrupting the association of PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly and reducing H3K27me3 marks on NOTCH pathway gene promoters. This epigenetically activates NOTCH signaling and maintains cancer stem cell subpopulations in colorectal cancer. Restoring the NOTCH pathway by expressing NICD1 or HES1 in STRAP-depleted cells reverses the CSC phenotype. |
Co-immunoprecipitation, ChIP-seq, siRNA knockdown, lentiviral rescue, in vitro and in vivo tumor assays |
Cancer research |
High |
28827371
|
| 2018 |
STRAP interacts with MELK (maternal embryonic leucine zipper kinase) and their association is phosphorylation-dependent. Sanguinarine dephosphorylates STRAP and MELK and disrupts their interaction, triggering Bax-dependent intrinsic apoptosis in colorectal cancer cells. |
Co-immunoprecipitation, immunofluorescence, in vitro kinase activity assay, western blotting, in vivo orthotopic model |
BMC cancer |
Medium |
29783958
|
| 2018 |
Strap associates with Csde1 (Cold shock domain protein e1/Unr) in erythroblasts and is the most strongly associated protein with Csde1. Reduced Strap expression alters mRNA and/or protein expression of several Csde1-bound transcripts involved in translational regulation during hypoxia (Hmbs, eIF4g3, Pabpc4), as well as Vim and Elavl1, without altering the overall pool of Csde1-bound transcripts. |
Co-immunoprecipitation, mass spectrometry, RIP (RNA immunoprecipitation), siRNA knockdown, proteomics |
PloS one |
Medium |
30138317
|
| 2019 |
During autophagy, TTC5/STRAP binds JMY and antagonizes JMY's actin nucleation activity. LC3 recruits JMY to the phagophore and promotes its actin nucleation activity. An in vitro reconstitution system demonstrated that membrane-bound LC3 is sufficient to recruit JMY and stimulate JMY-mediated actin filament assembly, while STRAP acts as a negative autophagy regulator by competing with this activation. |
In vitro reconstitution, co-immunoprecipitation, actin nucleation assay |
Autophagy |
High |
30593260
|
| 2020 |
STRAP was identified as a spliceosome-associated factor. Upon Strap deletion, numerous alternative splicing events occur in mouse embryoid bodies undergoing neuroectoderm-like differentiation. Global mapping by eCLIP-seq in mouse embryos reveals STRAP preferentially targets transcripts for nervous system development and regulates alternative splicing through preferred binding positions. STRAP is involved in the assembly of 17S U2 snRNP proteins. In Xenopus, loss of Strap impedes lineage differentiation, delays neural tube closure, and alters exon skipping. |
eCLIP-seq, STRAP-knockout mouse embryoid bodies, Xenopus loss-of-function, U2 snRNP assembly assay, RNA-seq splicing analysis |
Nature communications |
High |
33230114
|
| 2020 |
GDF5 increases expression of STRAP and NME1 in SH-SY5Y neuronal cells. Expression of both STRAP and NME1 is necessary and sufficient for the promotion of neurite growth by GDF5 in SH-SY5Y cells and in cultured midbrain dopaminergic neurons. |
Proteomics, siRNA knockdown, overexpression, neurite length quantification |
iScience |
Medium |
32853992
|
| 2020 |
STRAP is acetylated at lysines 147, 148, and 156 by the acetyltransferases CBP. The deacetylase SIRT7 reverses this acetylation. Hypo- or hyperacetylation mutations (3KR or 3KQ) of STRAP influence its activation and stabilization of p53. Following 5-FU treatment, STRAP is mobilized from the cytoplasm to the nucleus and promotes STRAP acetylation. |
Mass spectrometry identification of acetylation sites, mutagenesis, co-immunoprecipitation, subcellular fractionation, p53 functional assays |
International journal of molecular sciences |
High |
32527012
|
| 2024 |
circPCNXL2 directly binds STRAP and induces interaction between STRAP and MEK1/2, resulting in activation of ERK/MAPK pathways and tumor promotion in intrahepatic cholangiocarcinoma. |
RNA pulldown, mass spectrometry, RIP (RNA immunoprecipitation), co-immunoprecipitation, luciferase reporter, xenograft model |
Molecular cancer |
Medium |
38365721
|
| 2025 |
The deubiquitinase USP38 stabilizes STRAP via deubiquitination, thereby enhancing TGF-β/SMAD signaling and promoting atrial fibrosis in chronic kidney disease-associated atrial fibrillation. STRAP knockdown reverses the pro-fibrotic effects induced by USP38 overexpression. |
Co-immunoprecipitation, ubiquitination assay, cardiomyocyte-specific knockout/overexpression mice, immunofluorescence, STRAP knockdown rescue |
Molecular medicine |
High |
40514673
|
| 2025 |
The Csde1-Strap complex binds Bach2 mRNA and couples its decay with translation to control the magnitude and duration of Bach2 protein expression during B cell differentiation. In the absence of Csde1 or Strap, Bach2 translation is decoupled from mRNA decay, leading to elevated and prolonged Bach2 protein expression and impaired plasma cell differentiation. |
RNA interactome capture, CRISPR/Cas9 screening, RIP, co-immunoprecipitation, mRNA decay assays, polysome profiling |
Nature communications |
High |
40133358
|
| 2026 |
iNOS mediates S-nitrosylation of STRAP specifically at Cys152 and Cys270. S-nitrosylation disrupts the STRAP-ASK1 interaction, increases ASK1 activity, activates the MKK3-p38 pathway, and enhances hydrogen peroxide-induced apoptosis. Mutation of Cys152/270 to serine abolishes the STRAP-ASK1 interaction and constitutively activates the ASK1-MKK3-p38 pathway. STRAP specifically interacts with iNOS but not eNOS or nNOS. |
S-nitrosylation assay (biotin switch), co-immunoprecipitation, mutagenesis, kinase activity assay, apoptosis assays, iNOS overexpression |
The Journal of biological chemistry |
High |
41519199
|
| 2005 |
Unrip (STRAP) is integrated into the SMN complex via a stable interaction with Gemin7. It is also found in a mutually exclusive complex with Unr. Unrip is absent from nuclear gems/Cajal bodies and localizes predominantly to the cytoplasm. RNAi-induced reduction of Unrip leads to enhanced accumulation of SMN in the nucleus and increased formation of nuclear gems/Cajal bodies. |
Co-immunoprecipitation, RNAi knockdown, immunofluorescence localization, biochemical fractionation |
Human molecular genetics |
High |
16159890
|
| 2005 |
Unrip (STRAP) directly interacts with Gemin6 and Gemin7 within the SMN complex, also binds a subset of Sm proteins, and unrip-containing SMN complexes are necessary and sufficient to mediate the assembly of spliceosomal snRNPs in vitro. |
Biochemical reconstitution of snRNP assembly, co-immunoprecipitation, pulldown assays |
FEBS letters |
High |
15848170
|
| 2009 |
p49/STRAP interacts with the β-sandwich domain of Hsp70. It reduces ATP-hydrolytic activity of Hsp70 stimulated by Hsp40 and inhibits the refolding activity of the Hsp70/Hsp40 chaperone system, functioning as a co-chaperone. |
Co-immunoprecipitation, ATPase assay, protein refolding assay, domain mapping |
Biochemical and biophysical research communications |
Medium |
19751705
|
| 2022 |
STRAP overexpression in neuroblastoma cell lines activates focal adhesion kinase (FAK) downstream targets as measured by kinomic peptide microarray. FAK inhibitor treatment selectively decreased growth of STRAP-overexpressing neuroblastoma cells compared to controls, placing STRAP upstream of FAK in a signaling pathway. |
Kinomic peptide microarray (PamChip), stable overexpression, FAK inhibitor (PF-573,228) treatment, proliferation assay |
Journal of pediatric surgery |
Medium |
35272839
|