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Role of GATA-1 in the regulation of C3G during platelet differentiation

AutorBaquero, Cristina; Palao, Nerea; Guerrero Arroyo, María del Carmen ; Porras, Almudena
Fecha de publicación2017
CitaciónFEBS3+ (2017)
XL SEBBM Congress (2017)
ResumenC3G (Crk SH3-domain-binding Guanine-nucleotide-exchange factor) is a guanine nucleotide exchange factor (GEF) for members of the Ras family, mainly Rap1. However, C3G can also act through mechanisms independent of its GEF activity. For example, to inhibit tumor transformation and to regulate apoptosis. C3G is involved in platelet activation and adhesion acting through Rap1. Previous studies from our group suggest that C3G/Rap1 pathway promotes megakaryocytic differentiation. In addition, our bioinformatic analyses revealed the existence of binding sequences for the hematopoietic transcription factor GATA-1 in C3G gene regulatory regions. Therefore, GATA-1 could be a potential regulator of C3G during megakaryocytic/platelet differentiation. To evaluate it, we have analyzed the effect of GATA-1 overexpression and silencing on C3G expression and megakaryocyte/platelet diff erentiation using the human megakaryoblast cell line, Dami (derived from a patient with megakaryoblastic leukemia). Our results indicate that GATA-1 overexpression induces C3G expression during megakaryocytic differentiation and promotes the polyploidization associated with this differentiation process induced by PMA. Moreover, GATA-1 knock-down decreases C3G expression and megakaryocytic differentiation. Altogether these data support that GATA-1, acting through C3G, induces the megakaryocytic/platelet diff erentiation process. To further characterize the implication of GATA-1/C3G pathway in megakaryocytic differentiation, a stable C3G knock-down has been generated in the promegakaryocytic Dami cell line.
DescripciónResumen del póster presentado al 1st Joint Meeting of the French-Portuguese-Spanish Biochemical and Molecular Biology Societies y al XL Spanish Society of Biochemistry and Molecular Biology (SEBBM) Congress, celebrado en Barcelona (España) del 23 al 26 de octubre de 2017.-- et al.
URIhttp://hdl.handle.net/10261/163985
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