Role of RAC3 coactivator in the adipocyte differentiation

LIRA, MARÍA CECILIA; ROSA, FRANCISCO DAMIÁN; PANELO L.C.; COSTAS M A; RUBIO M F

Cell Death and Discovery

Springer Nature

Año: 2018

RAC3 is a member of p160 family of Steroid Receptor Coactivators and it is highly expressed in several human cancers, contributing to enhanced cell proliferation and cellular transformation. In this work, we have studied the role of RAC3 during adipogenesis in L-929 cells. This is a highly regulated process, involving cell cycle arrest and change in the gene expression pattern required for morphological remodeling. We found that RAC3 expression levels are down regulated during specific stimulus induced-adipocyte differentiation. In addition, cells constitutively expressing low levels of RAC3 (shRNA), show a potentiated adipocyte differentiation shortening the time at which the adipocyte markers Perilipin, PPAR-γ and Oil Red O staining are detected. Moreover, the RAC3 down regulation favors cell arrest and autophagy. Early and late autophagy inhibitors block adipocyte differentiation of control cells, but partially inhibit the shRAC3 differentiation, demonstrating that although autophagy is required for adipogenesis, additional signals could be trigged by RAC3 down regulation. We conclude that RAC3 is a key regulator of adipogenesis, whose down regulation generates the cellular arrest and autophagic responses, both being required steps in the process.