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Original Article
PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate
Article first published online: 2 MAY 2007
DOI: 10.1002/jcp.21117
Copyright © 2007 Wiley-Liss, Inc.
Additional Information
How to Cite
Bohensky, J., Shapiro, I. M., Leshinsky, S., Watanabe, H. and Srinivas, V. (2007), PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate. J. Cell. Physiol., 213: 246–251. doi: 10.1002/jcp.21117
Publication History
- Issue published online: 19 JUL 2007
- Article first published online: 2 MAY 2007
- Manuscript Accepted: 26 MAR 2007
- Manuscript Received: 13 DEC 2006
Funded by
- National Institutes of Health. Grant Numbers: DE 015694, DE 016383, DE 010875, DE 013319
- Abstract
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- Cited By
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.