title: Conserved regulation of the Jak/STAT pathway by the endosomal protein asrij maintains stem cell potency.
abstract: Asrij/OCIAD1 is an endosomal protein expressed in stem cells and cardiovascular lineages and aberrantly expressed in several cancers. We show that dose-dependent modulation of cytokine-dependent JAK/STAT signaling by Asrij regulates mouse embryonic stem cell pluripotency as well as Drosophila hematopoietic stem cell maintenance. Furthermore, mouse asrij can substitute for Drosophila asrij, indicating that they are true homologs. We identify a conserved region of Asrij that is necessary and sufficient for vesicular localization and function. We also show that Asrij and STAT3 colocalize in endosomes and interact biochemically. We propose that Asrij provides an endosomal scaffold for STAT3 interaction and activation, and may similarly control other circuits that maintain stemness. Thus, Asrij provides a key point of control for spatial and kinetic regulation of stem cell signals.
authors: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India.
authors: Abhishek
authors: A
authors: Sinha
authors: Rohan J
authors: RJ
authors: Khadilkar
authors: Vinay K
authors: VK
authors: S
authors: Arghyashree
authors: A
authors: Roychowdhury Sinha
authors: Maneesha S
authors: MS
authors: Inamdar
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D017124:Conserved Sequence; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C570890:Asrij protein, Drosophila; D029721:Drosophila Proteins; C509434:Emi2 protein, mouse; D044783:F-Box Proteins; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; D053612:Janus Kinases
references: Nature. 2010 Jan 28;463(7280):464-73
references: 20110990
references: Gynecol Oncol. 2008 May;109(2):226-33
references: 18328549
references: Mol Biol Cell. 2003 Feb;14(2):417-31
references: 12589044
references: J Biol Chem. 1996 Nov 22;271(47):30136-43
references: 8939963
references: Nat Rev Mol Cell Biol. 2002 Aug;3(8):600-14
references: 12154371
references: Semin Cell Dev Biol. 2008 Aug;19(4):329-40
references: 18691663
references: Development. 2009 Oct;136(19):3215-22
references: 19710168
references: Nat Commun. 2012 May 08;3:817
references: 22569365
references: Biochem Biophys Res Commun. 2004 Nov 26;324(4):1264-73
references: 15504351
references: Dev Genes Evol. 2003 Apr;213(3):134-7
references: 12690451
references: Nat Rev Mol Cell Biol. 2011 Nov 23;13(1):53-60
references: 22108513
references: Science. 2000 Jun 2;288(5471):1635-40
references: 10834841
references: Nature. 2007 Mar 15;446(7133):325-8
references: 17361184
references: Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2285-9
references: 8134389
references: Dev Dyn. 2003 Aug;227(4):578-86
references: 12889067
references: J Biol Chem. 2002 Apr 5;277(14):12067-74
references: 11815625
references: Annu Rev Biochem. 2012;81:737-65
references: 22443931
references: J Biol Chem. 2006 Mar 17;281(11):7302-8
references: 16407171
references: PLoS One. 2012;7(3):e32777
references: 22412924
references: Cell Cycle. 2010 Jun 1;9(11):2160-9
references: 20505363
references: Cell. 2003 Oct 31;115(3):281-92
references: 14636556
references: Development. 2005 Jun;132(11):2521-33
references: 15857916
references: J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3
references: 15020666
references: Cancer Res. 2003 Mar 15;63(6):1270-9
references: 12649187
references: PLoS One. 2011;6(11):e27667
references: 22110713
references: Mol Cancer Ther. 2010 Jun;9(6):1709-18
references: 20515946
references: Circulation. 1996 Nov 15;94(10):2626-32
references: 8921810