|Activation of cell cycle arrest and apoptosis by the proto-oncogene Pim-2.|
|PMID: 22506047 Owner: NLM Status: MEDLINE|
|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.|
|Daphna Levy; Ateret Davidovich; Shahar Zirkin; Yulia Frug; Amos M Cohen; Sara Shalom; Jeremy Don|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-04-10|
|Title: PloS one Volume: 7 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2012|
|Created Date: 2012-04-16 Completed Date: 2012-10-17 Revised Date: 2013-06-26|
Medline Journal Info:
|Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States|
|Languages: eng Pagination: e34736 Citation Subset: IM|
|The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|
|APA/MLA Format Download EndNote Download BibTex|
Cell Line, Tumor
Cell Nucleus / genetics, metabolism
Cell Survival / genetics
Cyclin-Dependent Kinase 2 / genetics, metabolism
Cyclin-Dependent Kinase Inhibitor p57 / genetics, metabolism
Cytoplasm / genetics, metabolism
DNA-Binding Proteins / genetics, metabolism
Down-Regulation / genetics
E2F1 Transcription Factor / genetics, metabolism
G1 Phase Cell Cycle Checkpoints / genetics*
Melanoma, Experimental / genetics, metabolism
Nuclear Proteins / genetics, metabolism
Proteasome Endopeptidase Complex / genetics, metabolism
Protein Isoforms / genetics, metabolism
Protein-Serine-Threonine Kinases / genetics*, metabolism*
Proto-Oncogene Proteins / genetics*, metabolism*
Tumor Suppressor Proteins / genetics, metabolism
cdc25 Phosphatases / genetics, metabolism
|0/CDKN1C protein, human; 0/Cyclin-Dependent Kinase Inhibitor p57; 0/DNA-Binding Proteins; 0/E2F1 Transcription Factor; 0/Nuclear Proteins; 0/PIM2 protein, human; 0/Protein Isoforms; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 0/tumor suppressor protein p73; EC 22.214.171.124/Protein-Serine-Threonine Kinases; EC 126.96.36.199/Cyclin-Dependent Kinase 2; EC 188.8.131.52/CDC25A protein, human; EC 184.108.40.206/cdc25 Phosphatases; EC 220.127.116.11/Proteasome Endopeptidase Complex|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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