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Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

Borna, Simon, Drobek, Ales, Kralova, Jarmila, Glatzova, Daniela, Splichalova, Iva, Fabisik, Matej, Pokorna, Jana, Skopcova, Tereza, Angelisova, Pavla, Kanderova, Veronika, Starkova, Julia, Stanek, Petr, Matveichuk, Orest V., Pavliuchenko, Nataliia, Kwiatkowska, Katarzyna, Protty, Majd B., Tomlinson, Michael G., Alberich-Jorda, Meritxell, Korinek, Vladimir and Brdicka, Tomas 2020. Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis. Journal of Cellular and Molecular Medicine 24 (2) , pp. 1980-1992. 10.1111/jcmm.14895

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Abstract

WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley
ISSN: 1582-1838
Date of First Compliant Deposit: 1 May 2020
Date of Acceptance: 19 November 2019
Last Modified: 04 May 2020 14:45
URI: http://orca.cf.ac.uk/id/eprint/131370

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