Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis

R. C. Nayak; K. H. Chang; A. K. Singh; M. Kotliar; M. Desai; A. M. Wellendorf; M. Wunderlich; J. Bartram; B. Mizukawa; M. Cuadrado; P. Dexheimer; A. Barski; X. R. Bustelo; N. N. Nassar; J. A. Cancelas

doi:10.1038/s41467-022-30651-7

Nature Communications (Jun 2022)

Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis

R. C. Nayak,
K. H. Chang,
A. K. Singh,
M. Kotliar,
M. Desai,
A. M. Wellendorf,
M. Wunderlich,
J. Bartram,
B. Mizukawa,
M. Cuadrado,
P. Dexheimer,
A. Barski,
X. R. Bustelo,
N. N. Nassar,
J. A. Cancelas

Affiliations

R. C. Nayak: Hoxworth Blood Center, University of Cincinnati College of Medicine
K. H. Chang: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
A. K. Singh: Hoxworth Blood Center, University of Cincinnati College of Medicine
M. Kotliar: Epigenomics Data Analysis Core, Divisions of Allergy & Immunology and Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
M. Desai: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
A. M. Wellendorf: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
M. Wunderlich: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
J. Bartram: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
B. Mizukawa: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
M. Cuadrado: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca
P. Dexheimer: Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
A. Barski: Epigenomics Data Analysis Core, Divisions of Allergy & Immunology and Human Genetics, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
X. R. Bustelo: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca
N. N. Nassar: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine
J. A. Cancelas: Hoxworth Blood Center, University of Cincinnati College of Medicine

DOI: https://doi.org/10.1038/s41467-022-30651-7
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 16

Abstract

Read online

Ph+ and Ph-like B-ALL remain poor prognosis leukemias. VAV3, a guanine nucleotide exchange factor, is activated and overexpressed in these leukemias. Here the authors reveal that leukemic VAV3 is predominantly nuclear. Nuclear VAV3, through its guanine nucleotide exchange factor and its effector nuclear RAC2, controls the repressive transcriptional activity of the polycomb repression complex-1 via nuclear AKT/PHLPP2 regulated BMI1.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

About the journal