Dynamic changes of p27(kip1) and Skp2 expression in injured rat sciatic nerve.

Abstract

S phase kinase-associated protein 2 (Skp2), an F-box protein, is required for the ubiquitination and consequent degradation of p27(kip1). Previous reports have showed that p27(kip1 )played important roles in cell cycle regulation and neurogenesis in the developing central nervous system. But the distribution and function of p27(kip1 )and Skp2 in nervous system lesion and regeneration remains unclear. In this study, we observed that they were expressed mainly in both Schwann cells and axons in adult rat sciatic nerve. Sciatic nerve crush and transection resulted in a significant up-regulation of Skp2 and a down-regulation of p27(kip1). By immunochemistry, we found that in the distal stumps of transected nerve from the end to the edge, the appearance of Skp2 in the edge is coincided with the decrease in p27(kip1) levels. Changes of them were inversely correlated. Results obtained by coimmunoprecipitation and double labeling further showed their interaction in the regenerating process. Thus, these results indicate that p27(kip1 )and Skp2 likely play an important role in peripheral nerve injury and regeneration.