PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate

✍ Scribed by Jolene Bohensky; Irving M. Shapiro; Serge Leshinsky; Hitoshi Watanabe; Vickram Srinivas

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 220 KB
• Volume: 213
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21117

✦ Synopsis

Abstract

The overall goal of the investigation was to examine the activity and role of the PIM serine/threonine protein kinases in the growth plate. We showed for the first time that PIM‐2 was highly expressed in epiphyseal chondrocytes and that the kinase was required for critical activities linked to cell survival. These activities were independent of those mediated by Akt‐1. It was noted that PIM‐2 protected chondrocytes from rapamycin sensitized (TOR inhibited) cell death. Since inhibition of mTOR caused autophagy, we examined the autophagic response of PIM‐2 silenced cells. We showed that PIM‐2 promoted expression and organization of autophagic proteins LC3, and Beclin‐1 and enhanced lysosomal acidification. At the same time, PIM‐2 modulated the activity of a key regulator of apoptosis, BAD. Since BAD inhibition and Beclin‐1 expression activated autophagy, it is likely that induction of the autophagic pathway would serve to inhibit apoptosis and preserve the life of the terminally differentiated chondrocyte. We conclude that PIM‐2 regulates a new intermediate stage in the differentiation pathway, the induction of autophagy. J. Cell. Physiol. 213: 246–251, 2007. © 2007 Wiley‐Liss, Inc.