Pim-2是作为一种丝氨酸/苏氨酸激酶于1984年首次被发现的，与癌细胞幸存和生长作用有关。之前的研究表明，高水平的PIM-2与各种恶性肿瘤紧密相关。
在人类细胞中，PIM-2的转录产物主要是两种蛋白异构体，它们的大小分别是34及41kDa。实验发现，它们都有相同的催化位点，但是蛋白质的N端却不同。
近日，以色列希伯来大学的研究人员发现在所有测试的细胞系中，34kDa的PIM-2异构体在细胞核及细胞质里有不同的构型。
为了深入研究这种34kDa的PIM-2异构体在细胞内的作用，研究人员将N端有HA标签的这种异构体短暂表达于HeLa细胞。结果却导致了停滞在G1期的细胞以及凋亡细胞水平增加。但是这样的结果在有Flag标签的41kDa异构体的实验中没有获得。
G1停滞及凋亡作用，与CDK2 T14/Y15磷酸化的增加及蛋白酶体依赖的CDC25A的下调，与p57, E2F-1及p73上调密切相关。然而，对激酶失活（kinase-dead）的有HA标签的34kDa PIM-2的过表达并没有发现这样的作用效果。
在p73沉默的细胞使用p73显性抑制，或者是过表达34kDa的PIM-2，都表明了这些细胞周期停滞及凋亡作用都是p73依赖的。
该研究表明，虽然PIM-2能够作为一个有效的存活因子，但是它在特定的环境下也能表现出原癌基因的作用。相关论文发表在4月10日的PLoS ONE。（生物谷Deepblue编译）
doi: 10.1371/journal.pone.0034736
PMC:
PMID:
Activation of Cell Cycle Arrest and Apoptosis by the Proto-Oncogene Pim-2
Daphna Levy, Ateret Davidovich, Shahar Zirkin, Yulia Frug, Amos M. Cohen, Sara Shalom, Jeremy Don.
Potent survival effects have been ascribed to the serine/threonine kinase proto-oncogene PIM-2.Elevated levels of PIM-2 are associated with various malignancies.In human cells, a single Pim-2 transcript gives rise mainly to two protein isoforms (34, 41 kDa) that share an identical catalytic site but differ at their N-terminus, due to in-frame alternative translation initiation sites.In this study we observed that the 34 kDa PIM-2 isoform has differential nuclear and cytoplasmic forms in all tested cell lines, suggesting a possible role for the balance between these forms for PIM-2's function.To further study the cellular role of the 34 kDa isoform of PIM-2, an N-terminally HA-tagged form of this isoform was transiently expressed in HeLa cells. Surprisingly, this resulted in increased level of G1 arrested cells, as well as of apoptotic cells.These effects could not be obtained by a Flag-tagged form of the 41 kDa isoform.The G1 arrest and apoptotic effects were associated with an increase in T14/Y15 phosphorylation of CDK2 and proteasom-dependent down-regulation of CDC25A, as well as with up-regulation of p57, E2F-1, and p73. No such effects were obtained upon over-expression of a kinase-dead form of the HA-tagged 34 kDa PIM-2.By either using a dominant negative form of p73, or by over-expressing the 34 kDa PIM-2 in p73-silenced cells, we demonstrated that these effects were p73-dependent.These results demonstrate that while PIM-2 can function as a potent survival factor, it can, under certain circumstances, exhibit pro-apoptotic effects as well.
