{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:56:27Z","timestamp":1791237387226,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2008,3,28]]},"abstract":"<jats:p>\n            PICOT (protein kinase C\u2013interacting cousin of thioredoxin) was previously shown to inhibit pressure overload-induced cardiac hypertrophy, concomitant with an increase in ventricular function and cardiomyocyte contractility. The combined analyses of glutathione\n            <jats:italic>S<\/jats:italic>\n            -transferase pull-down experiments and mass spectrometry enabled us to determine that PICOT directly interacts with muscle LIM protein (MLP) via its carboxyl-terminal half (PICOT-C). It was also shown that PICOT colocalizes with MLP in the Z-disc. MLP is known to play a role in anchoring calcineurin to the Z-disc in the sarcomere, which is critical for calcineurin\u2013NFAT (nuclear factor of activated T cells) signaling. We, therefore, suggested that PICOT may affect calcineurin\u2013NFAT signaling through its interaction with MLP. Consistent with this hypothesis, PICOT, or more specifically PICOT-C, abrogated phenylephrine-induced increases in calcineurin phosphatase activity, NFAT dephosphorylation\/nuclear translocation, and NFAT-dependent transcriptional activation in neonatal cardiomyocytes. In addition, pressure overload\u2013induced upregulation of NFAT target genes was significantly diminished in the hearts of PICOT-overexpressing transgenic mice. PICOT interfered with MLP\u2013calcineurin interactions in a dose-dependent manner. Moreover, calcineurin was displaced from the Z-disc, concomitant with an abrogated interaction between calcineurin and MLP, in the hearts of PICOT transgenic mice. Replenishment of MLP restored the hypertrophic responses and the increase in calcineurin phosphatase activity that was inhibited by PICOT in phenylephrine-treated cardiomyocytes. Finally, PICOT-C inhibited cardiac hypertrophy to an extent that was comparable to that of full-length PICOT. Taken together, these data suggest that PICOT inhibits cardiac hypertrophy largely by negatively regulating calcineurin\u2013NFAT signaling via disruption of the MLP\u2013calcineurin interaction.\n          <\/jats:p>","DOI":"10.1161\/circresaha.107.165985","type":"journal-article","created":{"date-parts":[[2008,2,8]],"date-time":"2008-02-08T02:36:40Z","timestamp":1202438200000},"page":"711-719","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["PICOT Attenuates Cardiac Hypertrophy by Disrupting Calcineurin\u2013NFAT Signaling"],"prefix":"10.1161","volume":"102","author":[{"given":"Dongtak","family":"Jeong","sequence":"first","affiliation":[{"name":"From the Global Research Laboratory and Department of Life Science (D.J., J.M.K., H.C., J.G.O., W.J.P.), Gwangju Institute of Science and Technology, Gwangju, Korea; Cardiovascular Institute (J.P., R.J.H.), Mount Sinai School of Medicine of New York University; and Department of Medicine (S.-H.Y., E.-S. Ju, E.-S. Jeon), Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Myoung","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Global Research Laboratory and Department of Life Science (D.J., J.M.K., H.C., J.G.O., W.J.P.), Gwangju Institute of Science and Technology, Gwangju, Korea; Cardiovascular Institute (J.P., R.J.H.), Mount Sinai School of Medicine of New York University; and Department of Medicine (S.-H.Y., E.-S. Ju, E.-S. Jeon), Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeseon","family":"Cha","sequence":"additional","affiliation":[{"name":"From the Global Research Laboratory and Department of Life Science (D.J., J.M.K., H.C., J.G.O., W.J.P.), Gwangju Institute of Science and Technology, Gwangju, Korea; Cardiovascular Institute (J.P., R.J.H.), Mount Sinai School of Medicine of New York University; and Department of Medicine (S.-H.Y., E.-S. Ju, E.-S. Jeon), Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Gyun","family":"Oh","sequence":"additional","affiliation":[{"name":"From the Global Research Laboratory and Department of Life Science (D.J., J.M.K., H.C., J.G.O., W.J.P.), Gwangju Institute of Science and Technology, Gwangju, Korea; Cardiovascular Institute (J.P., R.J.H.), Mount Sinai School of Medicine of New York University; and Department of Medicine (S.-H.Y., E.-S. Ju, E.-S. Jeon), Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeho","family":"Park","sequence":"additional","affiliation":[{"name":"From the Global Research Laboratory and Department of Life Science (D.J., J.M.K., H.C., J.G.O., W.J.P.), Gwangju Institute of Science and Technology, Gwangju, Korea; Cardiovascular Institute (J.P., R.J.H.), Mount Sinai School of Medicine of New York University; and Department of Medicine (S.-H.Y., E.-S. Ju, E.-S. 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Jeon), Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Seon","family":"Ju","sequence":"additional","affiliation":[{"name":"From the Global Research Laboratory and Department of Life Science (D.J., J.M.K., H.C., J.G.O., W.J.P.), Gwangju Institute of Science and Technology, Gwangju, Korea; Cardiovascular Institute (J.P., R.J.H.), Mount Sinai School of Medicine of New York University; and Department of Medicine (S.-H.Y., E.-S. Ju, E.-S. 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