Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Identification of USP7 as an essential component to maintain integrity and function of non-canonical PRC1.1 in leukemia

Henny Maat, Jennifer Jaques, Aida Rodríguez López, Marcel P. de Vries, Chantal Gravesteijn, Annet Z. Brouwers-Vos, Gerwin Huls, Edo Vellenga, Vincent van den Boom, Jan Jacob Schuringa
doi: https://doi.org/10.1101/221093
Henny Maat
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer Jaques
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aida Rodríguez López
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marcel P. de Vries
2Department of Pharmacy, Interfaculty Mass Spectrometry Center, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands;
3Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chantal Gravesteijn
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annet Z. Brouwers-Vos
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerwin Huls
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edo Vellenga
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent van den Boom
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan Jacob Schuringa
1Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: j.j.schuringa@umcg.nl
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Polycomb proteins are essential epigenetic regulators of gene transcription. KDM2B, the chromatin-binding moiety of non-canonical PRC1.1, is critically important for human leukemias. Here, we investigated the complete interactome of KDM2B in human leukemic cells and identified that the deubiquitinase USP7 is an essential component of PRC1.1 and required for its stability and function. USP7 inhibition results in disassembly of the PRC1.1 complex and consequently loss of binding to its target loci. PRC1.1 can be associated with active loci and loss of PRC1.1 binding coincided with loss of H2AK119ub, reduced H3K27ac levels and reduced gene transcription, whereas H3K4me3 levels remained unaffected. Survival was reduced in (primary) acute myeloid leukemia cells in both cycling as well as quiescent populations upon USP7 inhibition, also independent of the USP7-MDM2-p53 axis. Finally, we evaluated the efficacy of USP7 inhibition in vivo and find that progression of MLL-AF9-induced leukemia is delayed, although in a niche-dependent manner.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 17, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Identification of USP7 as an essential component to maintain integrity and function of non-canonical PRC1.1 in leukemia
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Identification of USP7 as an essential component to maintain integrity and function of non-canonical PRC1.1 in leukemia
Henny Maat, Jennifer Jaques, Aida Rodríguez López, Marcel P. de Vries, Chantal Gravesteijn, Annet Z. Brouwers-Vos, Gerwin Huls, Edo Vellenga, Vincent van den Boom, Jan Jacob Schuringa
bioRxiv 221093; doi: https://doi.org/10.1101/221093
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Identification of USP7 as an essential component to maintain integrity and function of non-canonical PRC1.1 in leukemia
Henny Maat, Jennifer Jaques, Aida Rodríguez López, Marcel P. de Vries, Chantal Gravesteijn, Annet Z. Brouwers-Vos, Gerwin Huls, Edo Vellenga, Vincent van den Boom, Jan Jacob Schuringa
bioRxiv 221093; doi: https://doi.org/10.1101/221093

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3502)
  • Biochemistry (7343)
  • Bioengineering (5319)
  • Bioinformatics (20258)
  • Biophysics (10008)
  • Cancer Biology (7735)
  • Cell Biology (11293)
  • Clinical Trials (138)
  • Developmental Biology (6434)
  • Ecology (9947)
  • Epidemiology (2065)
  • Evolutionary Biology (13315)
  • Genetics (9359)
  • Genomics (12579)
  • Immunology (7696)
  • Microbiology (19008)
  • Molecular Biology (7437)
  • Neuroscience (41011)
  • Paleontology (300)
  • Pathology (1228)
  • Pharmacology and Toxicology (2134)
  • Physiology (3155)
  • Plant Biology (6858)
  • Scientific Communication and Education (1272)
  • Synthetic Biology (1895)
  • Systems Biology (5311)
  • Zoology (1087)