The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG.

Animals Male Mice Co-Repressor Proteins Gene Expression Regulation Genes, Regulator Leukemia Transcription Factors

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
21 09 2023
Historique:
received: 07 03 2022
accepted: 16 08 2023
medline: 25 9 2023
pubmed: 22 9 2023
entrez: 22 9 2023
Statut: epublish

Résumé

The ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3' end of the PNT (pointed) domain, in ERG's ability to induce leukemia. P199 is necessary for ERG to promote self-renewal, prevent myeloid differentiation in hematopoietic progenitor cells, and initiate leukemia in mouse models. Here we show that P199 facilitates ERG's interaction with the NCoR-HDAC3 co-repressor complex. Inhibiting HDAC3 reduces the growth of ERG-dependent leukemic and prostate cancer cells, indicating that the interaction between ERG and the NCoR-HDAC3 co-repressor complex is crucial for its oncogenic activity. Thus, targeting this interaction may offer a potential therapeutic intervention.

Identifiants

DOI: 10.1038/s41467-023-41067-2 PMID: 37735473 PMC: PMC10514085
pubmed: 37735473
doi: 10.1038/s41467-023-41067-2
pii: 10.1038/s41467-023-41067-2
pmc: PMC10514085
doi:

Substances chimiques

Co-Repressor Proteins 0
Transcription Factors 0
histone deacetylase 3 EC 3.5.1.98
Ncor1 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5871

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Eitan Kugler (E)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.

Shreyas Madiwale (S)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Darren Yong (D)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

Julie A I Thoms (JAI)

Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
School of Biomedical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
ORCID: 0000-0002-4876-7230

Yehudit Birger (Y)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

David B Sykes (DB)

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA & Harvard Stem Cell Institute, Cambridge, MA, USA.
ORCID: 0000-0002-9788-0221

Johannes Schmoellerl (J)

Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
ORCID: 0000-0002-8461-8881

Aneta Drakul (A)

Division of Pediatric Oncology, and Children Research Center, University Children's Hospital, Zurich, Switzerland.

Valdemar Priebe (V)

Division of Pediatric Oncology, and Children Research Center, University Children's Hospital, Zurich, Switzerland.

Muhammad Yassin (M)

Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Nasma Aqaqe (N)

Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Avigail Rein (A)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Hila Fishman (H)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Ifat Geron (I)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Chun-Wei Chen (CW)

Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
ORCID: 0000-0002-8737-6830

Brian Raught (B)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Qiao Liu (Q)

Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.

Heather Ogana (H)

Department of Pediatrics, Division of Hematology and Oncology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.

Elisabeth Liedke (E)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0003-2525-611X

Jean-Pierre Bourquin (JP)

Division of Pediatric Oncology, and Children Research Center, University Children's Hospital, Zurich, Switzerland.

Johannes Zuber (J)

Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
Medical University of Vienna, Vienna, Austria.
ORCID: 0000-0001-8810-6835

Michael Milyavsky (M)

Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
ORCID: 0000-0002-5083-0809

John Pimanda (J)

Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
School of Biomedical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
ORCID: 0000-0002-0509-8962

Gilbert G Privé (GG)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Gil.Prive@uhnresearch.ca.
Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Gil.Prive@uhnresearch.ca.
ORCID: 0000-0002-0712-4319

Shai Izraeli (S)

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. sizraeli@gmail.com.
The Rina Zaizov Pediatric Hematology and Oncology Division Schneider Children's Medical Center of Israel, Petach Tikva, Israel. sizraeli@gmail.com.
ORCID: 0000-0002-6938-2540

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › The NCOR-HDAC3 co-repressive complex modulates...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The NCOR-HDAC3 co-repressive complex modulates...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines corépressives › The NCOR-HDAC3 co-repressive complex modulates...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › The NCOR-HDAC3 co-repressive complex modulates...
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes régulateurs › The NCOR-HDAC3 co-repressive complex modulates...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Leucémies › The NCOR-HDAC3 co-repressive complex modulates...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › The NCOR-HDAC3 co-repressive complex modulates...