Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis.
Simon BornaAles DrobekJarmila KralovaDaniela GlatzovaIva SplichalovaMatej FabisikJana PokornaTereza SkopcovaPavla AngelisovaVeronika KanderovaJulia StarkovaPetr StanekOrest V MatveichukNataliia PavliuchenkoKatarzyna KwiatkowskaMajd B ProttyMichael G TomlinsonMeritxell Alberich-JordaVladimir KorinekTomas BrdickaPublished in: Journal of cellular and molecular medicine (2019)
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.
Keyphrases
- binding protein
- bone marrow
- poor prognosis
- cell migration
- single cell
- transcription factor
- induced apoptosis
- acute lymphoblastic leukemia
- liver failure
- mesenchymal stem cells
- small molecule
- respiratory failure
- oxidative stress
- long non coding rna
- intensive care unit
- hepatitis b virus
- artificial intelligence
- acute respiratory distress syndrome