UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A non-canonical ESCRT pathway, including His domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC Class I

Parkinson, MDJ; Piper, SC; Bright, NA; Evans, JL; Boname, JM; Bowers, K; Lehner, PJ; (2015) A non-canonical ESCRT pathway, including His domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC Class I. Biochemical Journal , 471 (1) pp. 79-88. 10.1042/BJ20150336. Green open access

[thumbnail of 79.full.pdf]
Preview
Text
79.full.pdf

Download (1MB) | Preview

Abstract

The Kaposi’s sarcoma-associated herpes virus (KSHV) K3 viral gene product effectively down-regulates cell surface MHC Class I. K3 is an E3 ubiquitin ligase that promotes K63-linked polyubiquitination of MHC Class I, providing the signal for clathrin mediated endocytosis. Endocytosis is followed by sorting into the intralumenal vesicles (ILVs) of multivesicular bodies (MVBs) and eventual delivery to lysosomes. The sorting of MHC Class I into MVBs requires many individual proteins of the four endosomal sorting complexes required for transport (ESCRTs). In HeLa cells expressing the KSHV K3 ubiquitin ligase, the effect of RNA interference-mediated depletion of individual proteins of the ESCRT-0 and ESCRT-I complexes and three ESCRT-III proteins showed that these are required to down-regulate MHC Class I. However, depletion of proteins of the ESCRT-II complex or of the ESCRT-III protein, VPS20/CHMP6, failed to prevent the loss of MHC Class I from the cell surface. Depletion of His domain phosphotyrosine phosphatase (HD-PTP) resulted in an increase in the cell surface concentration of MHC Class I in HeLa cells expressing the KSHV K3 ubiquitin ligase. Rescue experiments with wild type and mutant HD-PTP supported the conclusion that HD-PTP acts as an alternative to ESCRT-II and VPS20/CHMP6 as a link between the ESCRT-I and those ESCRT-III protein(s) necessary for ILV formation. Thus, the down-regulation of cell surface MHC Class I, polyubiquitinated by the KSHV K3 ubiquitin ligase, does not employ the canonical ESCRT pathway, but instead utilizes an alternative pathway in which HD-PTP replaces ESCRT-II and VPS20/CHMP6.

Type: Article
Title: A non-canonical ESCRT pathway, including His domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC Class I
Open access status: An open access version is available from UCL Discovery
DOI: 10.1042/BJ20150336
Publisher version: http://dx.doi.org/10.1042/BJ20150336
Language: English
Additional information: c 2015 Authors. This is an open access article published by Portland Press Limited and distributed under the Creative Commons Attribution License 3.0.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Security and Crime Science
URI: https://discovery.ucl.ac.uk/id/eprint/1470409
Downloads since deposit
35Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item