Evidence map›Paper›PMID 26221024›Full record

ArticleThe Biochemical journal2015

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

Michael D J Parkinson, Siân C Piper, Nicholas A Bright, Jennifer L Evans, Jessica M Boname, Katherine Bowers, Paul J Lehner, J Paul Luzio

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025
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  9. Journal of fungi (Basel, Switzerland) · 2023
    Article
  10. Exosomal transmission of viruses, a two-edged biological sword.Cell communication and signaling : CCS · 2023
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Life in the lumen: The multivesicular endosome.Traffic (Copenhagen, Denmark) · 2020
    Review
  20. RNA Interference-Mediated Inhibition of ESCRT in Mammalian Cells.Methods in molecular biology (Clifton, N.J.) · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Michael D J ParkinsonDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
Siân C PiperDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
Nicholas A BrightDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
Jennifer L EvansDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
Jessica M BonameDepartment of Medicine, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
Katherine BowersDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
Paul J LehnerDepartment of Medicine, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K.
J Paul LuzioDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Biomedical Campus, Hills Road, Cambridge, CB2 0XY, U.K. JPL10@cam.ac.uk.
Wellcome/MRC Cambridge Stem Cell Institute · GB

Funding

British Heart Foundation FS/02/045Medical Research Council G0900113Medical Research Council MR/M010007/1Wellcome Trust 093026Wellcome Trust 100140Wellcome Trust 101835
6 · The paper itself

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 Lys(63)-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 RNAi-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 (vacuolar protein sorting 20)/CHMP6 (charged MVB protein 6), failed to prevent the loss of MHC class I from the cell surface. Depletion of histidine 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 (WT) 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.

Indexed as

Down-RegulationUbiquitinationEndosomal Sorting Complexes Required for TransportHeLa CellsHerpesvirus 8, HumanHistocompatibility Antigens Class IHumansProtein Tyrosine Phosphatases, Non-ReceptorViral ProteinsEndosomal Sorting Complexes Required for TransportHistocompatibility Antigens Class IK3 protein, Kaposi's sarcoma-associated herpesvirusProtein Tyrosine Phosphatases, Non-ReceptorPTPN23 protein, humanViral Proteinsendocytosisendosomal sorting complex required for transport (ESCRT)histidine domain phosphotyrosine phosphatase (HD-PTP)histidine-domain protein tyrosine phosphatase non-receptor type 23 (PTPN23)lysosomeubiquitination (ubiquitylation)

Identifiers

PMID26221024
PMCPMC4613529
OpenAlexW2256814646

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.