Document Detail

Activation of cell cycle arrest and apoptosis by the proto-oncogene Pim-2.
MedLine Citation:
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-10
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  e34736     Citation Subset:  IM    
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
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MeSH Terms
Apoptosis / genetics*
Cell Line
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*
HCT116 Cells
HEK293 Cells
HL-60 Cells
HT29 Cells
HeLa Cells
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
Reg. No./Substance:
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 Kinases; EC Kinase 2; EC protein, human; EC Phosphatases; EC Endopeptidase Complex

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