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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005318naa a2200469 4500
001oai:DiVA.org:uu-334429
003SwePub
008171123s2018 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:229464029
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3344292 URI
0247 a https://doi.org/10.18632/oncotarget.237882 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:2294640292 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Vanlandewijck, Michael,d 1982-u Karolinska Institutet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning,Integrated Cardio Metabolic Center, Novum, Karolinska Institute, Huddinge, Sweden4 aut0 (Swepub:uu)micva660
2451 0a The protein kinase SIK downregulates the polarity protein Par3
264 c 2017-12-31
264 1b Impact Journals, LLC,c 2018
338 a print2 rdacarrier
500 a Michael Vanlandewijck and Mahsa Shahidi Dadras contributed equally to this work.
520 a The multifunctional cytokine transforming growth factor β (TGFβ) controls homeostasis and disease during embryonic and adult life. TGFβ alters epithelial cell differentiation by inducing epithelial-mesenchymal transition (EMT), which involves downregulation of several cell-cell junctional constituents. Little is understood about the mechanism of tight junction disassembly by TGFβ. We found that one of the newly identified gene targets of TGFβ, encoding the serine/threonine kinase salt-inducible kinase 1 (SIK), controls tight junction dynamics. We provide bioinformatic and biochemical evidence that SIK can potentially phosphorylate the polarity complex protein Par3, an established regulator of tight junction assembly. SIK associates with Par3, and induces degradation of Par3 that can be prevented by proteasomal and lysosomal inhibition or by mutation of Ser885, a putative phosphorylation site on Par3. Functionally, this mechanism impacts on tight junction downregulation. Furthermore, SIK contributes to the loss of epithelial polarity and examination of advanced and invasive human cancers of diverse origin displayed high levels of SIK expression and a corresponding low expression of Par3 protein. High SIK mRNA expression also correlates with lower chance for survival in various carcinomas. In specific human breast cancer samples, aneuploidy of tumor cells best correlated with cytoplasmic SIK distribution, and SIK expression correlated with TGFβ/Smad signaling activity and low or undetectable expression of Par3. Our model suggests that SIK can act directly on the polarity protein Par3 to regulate tight junction assembly.
650 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
650 7a NATURVETENSKAPx Biologix Cellbiologi0 (SwePub)106042 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Cell Biology0 (SwePub)106042 hsv//eng
7001 a Dadras, Mahsa Shahidiu Uppsala universitet,Ludwiginstitutet för cancerforskning,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)mahsh538
7001 a Lomnytska, Martau Uppsala universitet,Reproduktiv hälsa,Department of Oncology and Pathology, Karolinska Biomics Center, Karolinska Institute, Stockholm, Sweden4 aut0 (Swepub:uu)marlo829
7001 a Mahzabin, Tanzilau Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab,School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA, Australia4 aut
7001 a Lee Miller, Martinu Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark; Cancer Research UK, Cambridge Institute, University of Cambridge, Li Ka Shing Center, Cambridge, UK4 aut
7001 a Busch, Christeru Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut0 (Swepub:uu)chrbusch
7001 a Brunak, Sørenu Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark4 aut
7001 a Heldin, Carl-Henrik,d 1952-u Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Ludwiginstitutet för cancerforskning4 aut0 (Swepub:uu)carlheld
7001 a Moustakas, Aristidisu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Ludwiginstitutet för cancerforskning4 aut0 (Swepub:uu)arimo287
7102 a Uppsala universitetb Science for Life Laboratory, SciLifeLab4 org
7730 t Oncotargetd : Impact Journals, LLCg 9, s. 5716-5735q 9<5716-5735x 1949-2553
8564 u http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=23788&path%5B%5D=74849
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-334429
8564 8u https://doi.org/10.18632/oncotarget.23788
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:229464029

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