Identification and characterization of nuclear localization signal of pRS1 protein [Elektronische Ressource] / vorgelegt von Marina Leyerer

Identification and characterization of Nuclear Localization Signal of pRS1 protein Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayrischen Julius-Maximilians-Universität Würzburg vorgelegt von Marina Leyerer aus Nowosibirsk, Rußland Würzburg, 2007 Eingereicht am: Mitglieder der Promotionskommission: Vorsitzender: Gutachter: Gutachter: Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am: SUMMARY RS1, a gene product of RSC1A1, is critically involved in cell density-dependent transcriptional down-regulation of SGLT1 in LLC-PK cells and in the post-transcriptional 1down-regulation of SGLT1 in small intestine. RS1 inhibits the release of SGLT1 containing vesicles from the trans-Golgi network and migrates into the nucleus where it inhibits transcription of SGLT1. In the present work we identified a novel 21 amino acids-long nonconventional nuclear localization sequence (RS1 NLS) in porcine RS1 (pRS1) that is necessary and sufficient for nuclear targeting of pRS1. RS1 NLS is framed by two consensus sequences for phosphorylation which are responsible for confluence-dependent regulation of RS1 NLS: a casein kinase 2 (CK2) site in position 348 and a protein kinase C (PKC) site in position 370. Confluence-dependent nuclear targeting was observed with amino acids 342-374 (R-NLS-Reg).