{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:44:40Z","timestamp":1785872680553,"version":"3.56.0"},"reference-count":33,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Histidine triad nucleotide-binding protein 1 (HINT1) is a small and evolutionarily conserved HIT family protein with putative tumor suppressor function. It has been implicated in the negative regulation of several transcription factors, but a role for HINT1 in Myocardin-related transcription factor A (MRTF-A)\/serum response factor (SRF) signaling has not been described. Here, we examined whether HINT1 functionally interacts with MRTF-A in fibroblasts. HINT1 reduced MRTF-A-dependent reporter activity in a dose-dependent manner, whereas a histidine triad mutant did not. Repression by HINT1 was retained upon deletion of the N-terminal RPEL motifs of MRTF-A, indicating that the effect was not confined to the inhibition of Rho-actin signaling. In parallel, HINT1-WT increased the MRTF-A protein abundance, which required the C-terminal part of MRTF-A. Co-immunoprecipitation experiments revealed the physical association of HINT1 with MRTF-A, whereas the histidine triad mutant or a C-terminally truncated MRTF-A did not show complex formation. Thus, our work suggests that HINT1 acts as a negative regulator of MRTF-A-dependent transcription by binding to the MRTF-A C-terminal part, which appears to require the histidine triad region and is accompanied by a separable increase in MRTF-A abundance.<\/jats:p>","DOI":"10.1515\/hsz-2026-0143","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:00:31Z","timestamp":1785870031000},"source":"Crossref","is-referenced-by-count":0,"title":["Functional interaction of HINT1 with MRTF-A: complex formation, protein stabilisation and transcriptional repression"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5338-5393","authenticated-orcid":false,"given":"Marianne","family":"Stognienko","sequence":"first","affiliation":[{"name":"Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg , D-06114 , Halle (Saale) , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0400-0222","authenticated-orcid":false,"given":"Guido","family":"Posern","sequence":"additional","affiliation":[{"name":"Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg , D-06114 , Halle (Saale) , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026080419002582749_j_hsz-2026-0143_ref_001","doi-asserted-by":"crossref","unstructured":"Abramson, J., Adler, J., Dunger, J., Evans, R., Green, T., Pritzel, A., Ronneberger, O., Willmore, L., Ballard, A.J., Bambrick, J., et al.. 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Sci. 6: 1310\u20131322, https:\/\/doi.org\/10.1021\/acsptsci.3c00079.","DOI":"10.1021\/acsptsci.3c00079"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_004","doi-asserted-by":"crossref","unstructured":"Esnault, C., Stewart, A., Gualdrini, F., East, P., Horswell, S., Matthews, N., and Treisman, R. (2014). Rho-actin signaling to the MRTF coactivators dominates the immediate transcriptional response to serum in fibroblasts. Genes Dev. 28: 943\u2013958, https:\/\/doi.org\/10.1101\/gad.239327.114.","DOI":"10.1101\/gad.239327.114"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_005","doi-asserted-by":"crossref","unstructured":"Foster, C.T., Gualdrini, F., and Treisman, R. (2017). Mutual dependence of the MRTF-SRF and YAP-TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics. Genes Dev. 31: 2361\u20132375, https:\/\/doi.org\/10.1101\/gad.304501.117.","DOI":"10.1101\/gad.304501.117"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_006","doi-asserted-by":"crossref","unstructured":"Gau, D., Chawla, P., Eder, I., and Roy, P. (2022). Myocardin-related transcription factor\u2019s interaction with serum-response factor is critical for outgrowth initiation, progression, and metastatic colonization of breast cancer cells. FASEB Bioadv 4: 509\u2013523, https:\/\/doi.org\/10.1096\/fba.2021-00113.","DOI":"10.1096\/fba.2021-00113"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_007","doi-asserted-by":"crossref","unstructured":"Geneste, O., Copeland, J.W., and Treisman, R. (2002). LIM kinase and diaphanous cooperate to regulate serum response factor and actin dynamics. J.\u00a0Cell Biol. 157: 831\u2013838, https:\/\/doi.org\/10.1083\/jcb.200203126.","DOI":"10.1083\/jcb.200203126"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_008","doi-asserted-by":"crossref","unstructured":"Genovese, G., Ghosh, P., Li, H., Rettino, A., Sioletic, S., Cittadini, A., and Sgambato, A. (2012). The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional activity in melanoma cells. Cell Cycle 11: 2206\u20132215, https:\/\/doi.org\/10.4161\/cc.20765.","DOI":"10.4161\/cc.20765"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_009","doi-asserted-by":"crossref","unstructured":"Gerstberger, S., Jiang, Q., and Ganesh, K. (2023). Metastasis. Cell 186: 1564\u20131579, https:\/\/doi.org\/10.1016\/j.cell.2023.03.003.","DOI":"10.1016\/j.cell.2023.03.003"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_010","doi-asserted-by":"crossref","unstructured":"He, H., Wang, D., Yao, H., Wei, Z., Lai, Y., Hu, J., Liu, X., Wang, Y., Zhou, H., Wang, N., et al.. (2015). Transcriptional factors p300 and MRTF-A synergistically enhance the expression of migration-related genes in MCF-7 breast cancer cells. Biochem. Biophys. Res. Commun. 467: 813\u2013820, https:\/\/doi.org\/10.1016\/j.bbrc.2015.10.060.","DOI":"10.1016\/j.bbrc.2015.10.060"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_011","doi-asserted-by":"crossref","unstructured":"Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Zidek, A., Potapenko, A., et al.. (2021). Highly accurate protein structure prediction with AlphaFold. Nature 596: 583\u2013589, https:\/\/doi.org\/10.1038\/s41586-021-03819-2.","DOI":"10.1038\/s41586-021-03819-2"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_012","doi-asserted-by":"crossref","unstructured":"Jung, T.Y., Jin, G.R., Koo, Y.B., Jang, M.M., Kim, C.W., Lee, S.Y., Kim, H., Lee, C.Y., Lee, S.Y., Ju, B.G., et al.. (2020). Deacetylation by SIRT1 promotes the tumor-suppressive activity of HINT1 by enhancing its binding capacity for \u03b2-catenin or MITF in colon cancer and melanoma cells. Exp. Mol. Med. 52: 1075\u20131089, https:\/\/doi.org\/10.1038\/s12276-020-0465-2.","DOI":"10.1038\/s12276-020-0465-2"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_013","doi-asserted-by":"crossref","unstructured":"Lee, Y.N., Nechushtan, H., Figov, N., and Razin, E. (2004). The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in Fc\u03b5RI-activated mast cells. Immu. 20: 145\u2013151, https:\/\/doi.org\/10.1016\/s1074-7613(04)00020-2.","DOI":"10.1016\/S1074-7613(04)00020-2"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_014","doi-asserted-by":"crossref","unstructured":"Lee, T.I. and Young, R.A. (2013). Transcriptional regulation and its misregulation in disease. Cell 152: 1237\u20131251, https:\/\/doi.org\/10.1016\/j.cell.2013.02.014.","DOI":"10.1016\/j.cell.2013.02.014"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_015","doi-asserted-by":"crossref","unstructured":"Leitner, L., Shaposhnikov, D., Mengel, A., Descot, A., Julien, S., Hoffmann, R., and Posern, G. (2011). MAL\/MRTF-A controls migration of non-invasive cells by upregulation of cytoskeleton-associated proteins. J.\u00a0Cell Sci. 124: 4318\u20134331, https:\/\/doi.org\/10.1242\/jcs.092791.","DOI":"10.1242\/jcs.092791"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_016","doi-asserted-by":"crossref","unstructured":"Luchsinger, L.L., Patenaude, C.A., Smith, B.D., and Layne, M.D. (2011). Myocardin-related transcription factor-A complexes activate type I collagen expression in lung fibroblasts. J.\u00a0Biol. Chem. 286: 44116\u201344125, https:\/\/doi.org\/10.1074\/jbc.M111.276931.","DOI":"10.1074\/jbc.M111.276931"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_017","doi-asserted-by":"crossref","unstructured":"Medjkane, S., Perez-Sanchez, C., Gaggioli, C., Sahai, E., and Treisman, R. (2009). Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis. Nat. Cell Biol. 11: 257\u2013268, https:\/\/doi.org\/10.1038\/ncb1833.","DOI":"10.1038\/ncb1833"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_018","doi-asserted-by":"crossref","unstructured":"Miralles, F., Posern, G., Zaromytidou, A.I., and Treisman, R. (2003). Actin dynamics control SRF activity by regulation of its coactivator MAL. 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Signal 4: ra40, https:\/\/doi.org\/10.1126\/scisignal.2001750.","DOI":"10.1126\/scisignal.2001750"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_021","doi-asserted-by":"crossref","unstructured":"Nielsen, J.C., Benito-Jardon, M., Christo Petrela, N., Diring, J., Bellamy, S., and Treisman, R. (2025). MRTF-dependent cytoskeletal dynamics drive efficient cell cycle progression. J.\u00a0Cell Sci. 138, https:\/\/doi.org\/10.1242\/jcs.264444.","DOI":"10.1101\/2025.06.06.657372"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_022","doi-asserted-by":"crossref","unstructured":"Onuh, J.O. and Qiu, H. (2021). Serum response factor-cofactor interactions and their implications in disease. FEBS J. 288: 3120\u20133134, https:\/\/doi.org\/10.1111\/febs.15544.","DOI":"10.1111\/febs.15544"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_023","doi-asserted-by":"crossref","unstructured":"Posern, G., Sotiropoulos, A., and Treisman, R. (2002). Mutant actins demonstrate a role for unpolymerized actin in control of transcription by serum response factor. Mol. Biol. Cell 13: 4167\u20134178, https:\/\/doi.org\/10.1091\/mbc.02-05-0068.","DOI":"10.1091\/mbc.02-05-0068"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_024","doi-asserted-by":"crossref","unstructured":"Shah, R.M., Maize, K.M., West, H.T., Strom, A.M., Finzel, B.C., and Wagner, C.R. (2018). Structure and functional characterization of human histidine triad nucleotide-binding protein 1 mutations associated with inherited axonal neuropathy with neuromyotonia. J.\u00a0Mol. Biol. 430: 2709\u20132721, https:\/\/doi.org\/10.1016\/j.jmb.2018.05.028.","DOI":"10.1016\/j.jmb.2018.05.028"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_025","doi-asserted-by":"crossref","unstructured":"Su, T., Suzui, M., Wang, L., Lin, C.S., Xing, W.Q., and Weinstein, I.B. (2003). Deletion of histidine triad nucleotide-binding protein 1\/PKC-interacting protein in mice enhances cell growth and carcinogenesis. Proc. Natl. Acad. Sci. U S A 100: 7824\u20137829, https:\/\/doi.org\/10.1073\/pnas.1332160100.","DOI":"10.1073\/pnas.1332160100"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_026","doi-asserted-by":"crossref","unstructured":"Vartiainen, M.K., Guettler, S., Larijani, B., and Treisman, R. (2007). Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Sci. 316: 1749\u20131752, https:\/\/doi.org\/10.1126\/science.1141084.","DOI":"10.1126\/science.1141084"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_027","doi-asserted-by":"crossref","unstructured":"Wang, J., Fang, P., Schimmel, P., and Guo, M. (2012). Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. J.\u00a0Phys. Chem. B 116: 6798\u20136805, https:\/\/doi.org\/10.1021\/jp212457w.","DOI":"10.1021\/jp212457w"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_028","doi-asserted-by":"crossref","unstructured":"Wang, L., Li, H., Zhang, Y., Santella, R.M., and Weinstein, I.B. (2009). HINT1 inhibits beta-catenin\/TCF4, USF2 and NF-\u03baB activity in human hepatoma cells. Int. J.\u00a0Cancer 124: 1526\u20131534, https:\/\/doi.org\/10.1002\/ijc.24072.","DOI":"10.1002\/ijc.24072"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_029","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhang, Y., Li, H., Xu, Z., Santella, R.M., and Weinstein, I.B. (2007). Hint1 inhibits growth and activator protein-1 activity in human colon cancer cells. Cancer Res. 67: 4700\u20134708, https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-4645.","DOI":"10.1158\/0008-5472.CAN-06-4645"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_030","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhou, M., and Jiang, L. (2023). The oncogenic and immunological roles of histidine triad nucleotide-binding protein 1 in human cancers and their experimental validation in the MCF-7 cell line. Ann. Transl. Med. 11: 147, https:\/\/doi.org\/10.21037\/atm-22-6637.","DOI":"10.21037\/atm-22-6637"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_031","doi-asserted-by":"crossref","unstructured":"Weiske, J. and Huber, O. (2005). The histidine triad protein Hint1 interacts with pontin and reptin and inhibits TCF-\u03b2-catenin-mediated transcription. J.\u00a0Cell Sci. 118: 3117\u20133129, https:\/\/doi.org\/10.1242\/jcs.02437.","DOI":"10.1242\/jcs.02437"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_032","doi-asserted-by":"crossref","unstructured":"Zhou, X., Chou, T.F., Aubol, B.E., Park, C.J., Wolfenden, R., Adams, J., and Wagner, C.R. (2013). Kinetic mechanism of human histidine triad nucleotide binding protein 1. Biochem. 52: 3588\u20133600, https:\/\/doi.org\/10.1021\/bi301616c.","DOI":"10.1021\/bi301616c"},{"key":"2026080419002582749_j_hsz-2026-0143_ref_033","doi-asserted-by":"crossref","unstructured":"Zimon, M., Baets, J., Almeida-Souza, L., De Vriendt, E., Nikodinovic, J., Parman, Y., Battaloglu, E., Matur, Z., Guergueltcheva, V., Tournev, I., et al.. (2012). Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. Nat. Genet. 44: 1080\u20131083, https:\/\/doi.org\/10.1038\/ng.2406.","DOI":"10.1038\/ng.2406"}],"container-title":["Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/hsz-2026-0143\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/hsz-2026-0143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:00:55Z","timestamp":1785870055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/hsz-2026-0143\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":33,"alternative-id":["10.1515\/hsz-2026-0143"],"URL":"https:\/\/doi.org\/10.1515\/hsz-2026-0143","relation":{},"ISSN":["1431-6730","1437-4315"],"issn-type":[{"value":"1431-6730","type":"print"},{"value":"1437-4315","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}