Abstract

14-3-3 protein family binds and regulate hundred of serine/threonine phosphorylated proteins. Considered as redundant, ubiquitous and constantly expressed this protein family was treated as an accessory for many signaling systems. Here we studied the reversible inhibition by acetylation of its essential N-{varepsilon}-lysine 49/51 residue during the osteogenic differentiation of human adipose-derived stem cells (ASC). We found that during the differentiation of ASC the levels of 14-3-3 acK49/51 increase showing that inhibition of 14-3-3 is necessary for this process. Among the 7 paralogs of this family, the inhibition by this posttranslational modification occurs mostly on the paralog {beta} located specifically in the nucleus where 14-3-3 was described to binds to H3 histone and many transcription factors. Short hairpin RNA silencing of 14-3-3{beta} gene but not 14-3-3{gamma} increases significantly the osteogenic potential of the cells. These results show that specifically 14-3-3{beta} is a negative regulator of osteogenesis and its inhibition by acetylation on lysine 51 is the cellular mechanism to regulate it.