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.
Highlights
WW domain binding protein 1-like (WBP1L) known as outcome predictor of acute leukaemia 1 (OPAL1) has attracted attention because of a report showing that its elevated expression at mRNA level correlates with favourable outcome in childhood acute lymphoblastic leukaemia (ALL).[1]
WW domain binding protein 1-like (WBP1L), 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
In addition and in agreement with previous reports of deregulated WBP1L expression in ETV6-RUNX1+ BCPALL, we have found elevated levels of WBP1L protein in REH cell line, which is derived from ETV6-RUNX1+ B cell progenitor ALL (BCP-ALL). (Figure 1C and S2A)
Summary
WW domain binding protein 1-like (WBP1L) known as outcome predictor of acute leukaemia 1 (OPAL1) has attracted attention because of a report showing that its elevated expression at mRNA level correlates with favourable outcome in childhood acute lymphoblastic leukaemia (ALL).[1]. Around 30 fusions of ETV6 to different partner genes and a number of mutations in ETV6 have been identified so far, many of them implicated in various haematological malignancies of myeloid and lymphoid origin.[7,8] In addition, its critical role in normal haematopoiesis has been revealed in studies of ETV6-deficient mice, which show profound defects in haematopoietic stem and progenitor cell function and inability of these cells to reconstitute haematopoiesis after bone marrow transplantation.[9,10]. We establish the role of WBP1L in CXCR4 signalling and in normal haematopoiesis. These findings form the basis for further research on its potential role in leukaemia
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