Vav1 plays an important role in the all-trans retinoic acid (ATRA)-induced completion of the differentiation program of acute promyelocytic leukemia (APL)-derived cells, in which it strengthens the drug effects and is involved in the regulation of maturation-related proteins, such as the CD11b surface antigen. In both myeloid and lymphoid cells, accumulating data attribute to the multidomain protein Vav1 a functional relevance in the control of gene expression, by direct interaction with chromatin remodeling and/or transcriptional proteins. The present study provides evidence that, in the APL-derived NB4 cell line, Vav1 and the transcription factor PU.1 cooperate in regulating the ATRA-induced CD11b expression. Both chromatin immunoprecipitation (ChIP) experiments and electrophoretic mobility shift assays (EMSA) indicate that Vav1 and PU.1 are recruited to CD11b promoter. Even if the two proteins may participate in diverse protein/DNA complexes, the amounts of complexes including PU.1 seem to be dependent on the interaction of this transcription factor with tyrosine-phosphorylated Vav1. The reported data suggest that the ATRA-induced increase of Vav1 expression and tyrosine phosphorylation may be involved in recruiting PU.1 to its consensus sequence on the CD11b promoter and, ultimately, in regulating CD11b expression during the late stages of neutrophil differentiation of APL-derived promyelocytes.
Vav1 and PU.1 are recruited to the CD11b promoter in APL-derived promyelocytes: Role of Vav1 in modulating PU.1-containing complexes during ATRA-induced differentiation
BRUGNOLI, Federica;LAMBERTINI, Elisabetta;PIVA, Maria Roberta;GRASSILLI, Silvia;CAPITANI, Silvano;BERTAGNOLO, Valeria
2010
Abstract
Vav1 plays an important role in the all-trans retinoic acid (ATRA)-induced completion of the differentiation program of acute promyelocytic leukemia (APL)-derived cells, in which it strengthens the drug effects and is involved in the regulation of maturation-related proteins, such as the CD11b surface antigen. In both myeloid and lymphoid cells, accumulating data attribute to the multidomain protein Vav1 a functional relevance in the control of gene expression, by direct interaction with chromatin remodeling and/or transcriptional proteins. The present study provides evidence that, in the APL-derived NB4 cell line, Vav1 and the transcription factor PU.1 cooperate in regulating the ATRA-induced CD11b expression. Both chromatin immunoprecipitation (ChIP) experiments and electrophoretic mobility shift assays (EMSA) indicate that Vav1 and PU.1 are recruited to CD11b promoter. Even if the two proteins may participate in diverse protein/DNA complexes, the amounts of complexes including PU.1 seem to be dependent on the interaction of this transcription factor with tyrosine-phosphorylated Vav1. The reported data suggest that the ATRA-induced increase of Vav1 expression and tyrosine phosphorylation may be involved in recruiting PU.1 to its consensus sequence on the CD11b promoter and, ultimately, in regulating CD11b expression during the late stages of neutrophil differentiation of APL-derived promyelocytes.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
