p57^kip2's role beyond Schwann cell cycle control

Abstract

The p57kip2 gene encodes a cyclin dependent kinase inhibitor that belongs to the Cip/Kip family of negative cell cycle regulators. Recently, experimental evidence emerged that beyond cell cycle control p57kip2 also regulates a number of different cellular processes. We found that in Schwann cells, these are the myelinating glial cells of the peripheral nervous system, small hairpin RNA dependent suppression of p57kip2 results in cell cycle exit and the initiation of the cellular differentiation program. Given that Schwann cells were so far regarded as being unable to differentiate in absence of axons, these were unexpected results. We thus concluded that p57kip2 is not involved in the control of Schwann cell proliferation but is a main intrinsic negative regulator of Schwann cell differentiation. Here we present GeneChip expression data which reveal the extent and complexity of cell cycle related gene regulations in p57kip2-suppressed Schwann cells. In addition, we provide experimental evidence that the differentiation promoting effect is at least partially mediated via p57kip2 / LIMK-1 interactions.