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.
- Klíčová slova
- CXCR4, ETV6, NEDD4 family, OPAL1, RUNX1, WBP1L, bone marrow homing, bone marrow transplantation, haematopoiesis, haematopoietic stem cell,
- MeSH
- adaptorové proteiny signální transdukční metabolismus MeSH
- glykoproteiny metabolismus MeSH
- HEK293 buňky MeSH
- hematopoetické kmenové buňky metabolismus MeSH
- hematopoéza * MeSH
- homeostáza MeSH
- lidé MeSH
- lipoylace MeSH
- malá interferující RNA metabolismus MeSH
- membránové proteiny genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- receptory CXCR4 metabolismus MeSH
- signální transdukce * MeSH
- ubikvitinace MeSH
- ubikvitinligasy metabolismus MeSH
- vazba proteinů MeSH
- zárodečné buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adaptorové proteiny signální transdukční MeSH
- glykoproteiny MeSH
- malá interferující RNA MeSH
- membránové proteiny MeSH
- receptory CXCR4 MeSH
- ubikvitinligasy MeSH
- WBP1L protein, human MeSH Prohlížeč
- Wbp1l protein, mouse MeSH Prohlížeč
