Vav1 in differentiation of tumoral promyelocytes

• Published in: Cellular signalling Vol. 24; no. 3; pp. 612 - 620
• Main Authors: Bertagnolo, Valeria, Brugnoli, Federica, Grassilli, Silvia, Nika, Ervin, Capitani, Silvano
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.03.2012
• Subjects: Actin Cytoskeleton; APL-derived cells; Cell Differentiation; Cell nucleus; Cell Nucleus - metabolism; Cell Nucleus - physiology; DNA-Binding Proteins - metabolism; Granulocyte Precursor Cells - cytology; Humans; Leukemia, Promyelocytic, Acute - metabolism; Leukemia, Promyelocytic, Acute - pathology; mRNA processing; Myeloid differentiation; Proto-Oncogene Proteins c-vav - metabolism; Proto-Oncogene Proteins c-vav - physiology; RNA, Messenger - metabolism; Transcription Factors - metabolism; Vav1; PMA; mRNA processing; Cell nucleus; LIC; GEF; AP-1; Vav1; Myeloid differentiation; NFAT; NF-κB; PIP; PIP3; PAK; ATRA; Actin cytoskeleton; APL; TMSB10; PIP2; Sfrs3; APL-derived cells
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2011.11.017

The multidomain protein Vav1, in addition to promote the acquisition of maturation related properties by normal hematopoietic cells, is a key player in the ATRA- and PMA-induced completion of the differentiation program of tumoral myeloid precursors derived from APL. This review is focussed on the role of Vav1 in differentiating promyelocytes, as part of interconnected networks of functionally related proteins ended to regulate different aspects of myeloid maturation. The role of Vav1 in determining actin cytoskeleton reorganization alternative to the best known function as a GEF for small G proteins is discussed, as well as the binding of Vav1 with cytoplasmic and nuclear signaling molecules which provides a new perspective in the modulation of nuclear architecture and activity. In particular, new hints are provided on the ability of Vav1 to determine the nuclear amount of proteins implicated in modulating mRNA production and stability and in regulating the ATRA-dependent protein expression also by direct interaction with transcription factors known to drive the ATRA-induced maturation of myeloid cells. The reviewed findings summarize the major advances in the understanding of additional, non conventional functions connected with the vast interactive potential of Vav1. [Display omitted] ► Vav1 sustains the agonist-induced maturation of APL-derived cells. ► Vav1 is responsible of GEF-independent modifications of cell and nuclear morphology. ► Vav1 drives inside the nucleus molecules involved in mRNA production and stability. ► Vav1 may be a target for anti-cancer strategies in hematological malignancies.