Conserved regulation of the JAK/STAT pathway by the endosomal protein Asrij maintains stem cell potency

Sinha, A., Khadilkar, R. J., K.S., V., Roychowdhury Sinha, A. and Inamdar, M. S. (2013) Conserved regulation of the JAK/STAT pathway by the endosomal protein Asrij maintains stem cell potency. Cell Reports, 4(4), pp. 649-658. (doi: 10.1016/j.celrep.2013.07.029) (PMID:23972987) (PMCID:PMC4673900)

Abstract

Summary: 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.

• Item Type: Articles
• Additional Information: This work was supported by the Department of Science and Technology and the Department of Biotechnology, Government of India, and the UK India Education and Research Initiative (UKIERI).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Roychowdhury Sinha, Dr Arghyashree
• Authors: Sinha, A., Khadilkar, R. J., K.S., V., Roychowdhury Sinha, A., and Inamdar, M. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2013 The Author(s)
• First Published: First published in Cell Reports 4(4):649-658
• Publisher Policy: Reproduced under a creative commons licence