Regulation of Stem Cell Proliferation by p38 MAPK Signaling

Abstract

The p38 Mitogen Activated Protein Kinase (MAPK) is a key member of a highly conserved superfamily of protein kinases. Mostly sensitive to inflammatory cytokines and stress signals, p38 activation leads to a variety of cellular responses, including proinflammatory cytokines secretion, cell survival, apoptosis induction and the regulation of cell proliferation. Here, we carried a focused investigation on the recent literature, across all systems and organisms, concerning the roles of p38 in the regulation of Stem Cell (SC) proliferation. Interestingly, we found that p38 can exert either a pro- or an anti- proliferative function, depending on the specific models and contexts. It is also activated by a variety of upstream signals and regulates SC proliferation through a wide diversity of molecular effectors. Whereas p38 regulates SC proliferation mostly cell-autonomously, an example of a non-cell autonomous p38-dependent regulation of SC proliferation was recently uncovered. Altogether, bringing together these recent findings improve our comprehension of the effects p38 has on SC proliferation, while these mechanisms and effectors appear as being conserved through evolution.