Essential role of hIST1 in cytokinesis

Agromayor, M., Carlton, J. G., Phelan, J. P., Matthews, D. R., Carlin, L. M. , Ameer-Beg, S., Bowers, K. and Martin-Serrano, J. (2009) Essential role of hIST1 in cytokinesis. Molecular Biology of the Cell, 20(5), pp. 1374-1387. (doi: 10.1091/mbc.E08-05-0474) (PMID:19129480) (PMCID:PMC2649264)

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The last steps of multivesicular body (MVB) formation, human immunodeficiency virus (HIV)-1 budding and cytokinesis require a functional endosomal sorting complex required for transport (ESCRT) machinery to facilitate topologically equivalent membrane fission events. Increased sodium tolerance (IST) 1, a new positive modulator of the ESCRT pathway, has been described recently, but an essential function of this highly conserved protein has not been identified. Here, we describe the previously uncharacterized KIAA0174 as the human homologue of IST1 (hIST1), and we report its conserved interaction with VPS4, CHMP1A/B, and LIP5. We also identify a microtubule interacting and transport (MIT) domain interacting motif (MIM) in hIST1 that is necessary for its interaction with VPS4, LIP5 and other MIT domain-containing proteins, namely, MITD1, AMSH, UBPY, and Spastin. Importantly, hIST1 is essential for cytokinesis in mammalian cells but not for HIV-1 budding, thus providing a novel mechanism of functional diversification of the ESCRT machinery. Last, we show that the hIST1 MIM activity is essential for cytokinesis, suggesting possible mechanisms to explain the role of hIST1 in the last step of mammalian cell division.

Item Type:Articles
Additional Information:This work was supported by Career Establishment grant G0400207 from the Medical Research Council UK.
Glasgow Author(s) Enlighten ID:Carlin, Dr Leo
Authors: Agromayor, M., Carlton, J. G., Phelan, J. P., Matthews, D. R., Carlin, L. M., Ameer-Beg, S., Bowers, K., and Martin-Serrano, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular Biology of the Cell
Publisher:American Society for Cell Biology
ISSN (Online):1939-4586
Published Online:07 January 2009

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