STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.

<h4>Background</h4>Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound heali...

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Autores principales:	Pankaj Goyal, Antje Behring, Abhishek Kumar, Wolfgang Siess
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57fa8748e35e4781aa02bc2fb9c8e108
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spelling	oai:doaj.org-article:57fa8748e35e4781aa02bc2fb9c8e1082021-11-18T07:00:11ZSTK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.1932-620310.1371/journal.pone.0016249https://doaj.org/article/57fa8748e35e4781aa02bc2fb9c8e1082011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283756/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1) phase have the highest potential to migrate. The molecular mechanism linking these two processes is not understood.<h4>Methodology/principal findings</h4>In this study, we explored the function of STK35L1, a novel Ser/Thr kinase, localized in the nucleus and nucleolus of endothelial cells. Molecular biological analysis identified a bipartite nuclear localization signal, and nucleolar localization sequences in the N-terminal part of STK35L1. Nuclear actin was identified as a novel binding partner of STK35L1. A class III PDZ binding domains motif was identified in STK35L1 that mediated its interaction with actin. Depletion of STK35L1 by siRNA lead to an accelerated G(1) to S phase transition after serum-stimulation of endothelial cells indicating an inhibitory role of the kinase in G(1) to S phase progression. Cell cycle specific genes array analysis revealed that one gene was prominently downregulated (8.8 fold) in STK35L1 silenced cells: CDKN2A alpha transcript, which codes for p16(INK4a) leading to G(1) arrest by inhibition of CDK4/6. Moreover in endothelial cells seeded on Matrigel, STK35L1 expression was rapidly upregulated, and silencing of STK35L1 drastically inhibited endothelial sprouting that is required for angiogenesis. Furthermore, STK35L1 depletion profoundly impaired endothelial cell migration in two wound healing assays.<h4>Conclusion/significance</h4>The results indicate that by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. The interaction of STK35L1 with nuclear actin might be critical in the regulation of these fundamental endothelial functions.Pankaj GoyalAntje BehringAbhishek KumarWolfgang SiessPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16249 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pankaj Goyal Antje Behring Abhishek Kumar Wolfgang Siess STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
description	<h4>Background</h4>Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1) phase have the highest potential to migrate. The molecular mechanism linking these two processes is not understood.<h4>Methodology/principal findings</h4>In this study, we explored the function of STK35L1, a novel Ser/Thr kinase, localized in the nucleus and nucleolus of endothelial cells. Molecular biological analysis identified a bipartite nuclear localization signal, and nucleolar localization sequences in the N-terminal part of STK35L1. Nuclear actin was identified as a novel binding partner of STK35L1. A class III PDZ binding domains motif was identified in STK35L1 that mediated its interaction with actin. Depletion of STK35L1 by siRNA lead to an accelerated G(1) to S phase transition after serum-stimulation of endothelial cells indicating an inhibitory role of the kinase in G(1) to S phase progression. Cell cycle specific genes array analysis revealed that one gene was prominently downregulated (8.8 fold) in STK35L1 silenced cells: CDKN2A alpha transcript, which codes for p16(INK4a) leading to G(1) arrest by inhibition of CDK4/6. Moreover in endothelial cells seeded on Matrigel, STK35L1 expression was rapidly upregulated, and silencing of STK35L1 drastically inhibited endothelial sprouting that is required for angiogenesis. Furthermore, STK35L1 depletion profoundly impaired endothelial cell migration in two wound healing assays.<h4>Conclusion/significance</h4>The results indicate that by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. The interaction of STK35L1 with nuclear actin might be critical in the regulation of these fundamental endothelial functions.
format	article
author	Pankaj Goyal Antje Behring Abhishek Kumar Wolfgang Siess
author_facet	Pankaj Goyal Antje Behring Abhishek Kumar Wolfgang Siess
author_sort	Pankaj Goyal
title	STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
title_short	STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
title_full	STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
title_fullStr	STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
title_full_unstemmed	STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
title_sort	stk35l1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/57fa8748e35e4781aa02bc2fb9c8e108
work_keys_str_mv	AT pankajgoyal stk35l1associateswithnuclearactinandregulatescellcycleandmigrationofendothelialcells AT antjebehring stk35l1associateswithnuclearactinandregulatescellcycleandmigrationofendothelialcells AT abhishekkumar stk35l1associateswithnuclearactinandregulatescellcycleandmigrationofendothelialcells AT wolfgangsiess stk35l1associateswithnuclearactinandregulatescellcycleandmigrationofendothelialcells
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STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.

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