PIM-2 is an independent chondrocyte survival and autophaqy in the epiphyseal growth plate
PIM-2 is an independent chondrocyte survival and autophaqy in the epiphyseal growth plate
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DOI：
10.1002/jcp.21117
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发表时间：
2007-10-01
影响因子：
5.6
通讯作者：
Srinivas, Vickram
中科院分区：
文献类型：
--
作者：
Bohensky, Jolene;Shapiro, Irving M.;Srinivas, Vickram
这项研究的总体目标是检查生长板中PIM丝氨酸/苏氨酸蛋白激酶的活性和作用。我们首次发现PIM-2在骨痂软骨细胞中高表达，并且该激酶是与细胞生存相关的关键活动所必需的。这些活性与Akt-I介导的活性无关。有人指出，PIM-2保护软骨细胞免受雷帕霉素致敏(TOR抑制)的细胞死亡。由于抑制mTOR导致自噬，我们检测了PIM-2沉默的细胞的自噬反应。我们发现PIM-2促进了自噬蛋白Lc3和Beclin-1的表达和组织，并增强了溶酶体的酸化。同时，PIM-2调节细胞凋亡的关键调节因子BAD的活性。由于BAD抑制和Beclin-1的表达激活了自噬，自噬途径的诱导很可能有助于抑制细胞凋亡和保护终末分化的软骨细胞的寿命。我们得出结论，PIM-2调节分化途径中的一个新的中间阶段，即自噬的诱导。(C)2007年Wiley-Liss，Inc.
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- I. 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. (c) 2007 Wiley-Liss, Inc.