TY - GEN
T1 - Dual Role of Pim-2 Depends on the Associated Proteome
AU - Levy, Daphna
AU - Cohen, Amos M.
AU - Don, Jeremy
N1 - Place of conference:N/A
PY - 2006
Y1 - 2006
N2 - Pim-2, a Ser/Thr kinase, is a proto-oncogene originally identified as common proviral insertion sites in T and B cell lymphomas in mice. Deregulation of Pim-2 expression has been documented in several human malignancies, including leukemia, lymphoma, multiple myeloma and prostate cancer. In human non-Hodgkin's lymphomas and in chronic lymphocytic leukemia Pim-2 is up-regulated and its expression correlates with disease activity. Pim-2 promotes cell survival in response to a wide variety of proliferative signals. Pim-2 promotes cell survival by phosphorylation of Bad and Cot. The goal of this study was to clarify the significance of our new unanticipated aspect of Pim-2′s function, namely, that over-expression of Pim-2 in HeLa cells led to cell cycle arrest at G1 and to increased apoptosis. We found that the G1 arrest was associated with increased (T14/Y15) phosphorylation of CDK2, increased proteosomic degradation of CDC25A, and increased levels of the CDK inhibitor p57. In addition, we found increased E2F-1 levels, which suggested the usage of the E2F-1 dependent apoptotic pathway. Using dominant negative forms of either E2F-1 or p73, which were co-expressed with Pim-2 in HeLa cells, revealed significant rescue of the G1 arrest and apoptotic phenomena. Silencing of Pim-2 in these cells, via siRNA, reversed the G1 arrest and pro-apoptotic effects, and verified the Pim-2 dependent specificity. We conclude that Pim-2 might play a dual role. Our data suggest that under certain environmental circumstances and in various cell types, Pim-2 appears to increase cell survival by abrogating some pro-apoptotic substrates, but under different proteomic associations Pim-2 might favor G1 arrest and apoptosis.
AB - Pim-2, a Ser/Thr kinase, is a proto-oncogene originally identified as common proviral insertion sites in T and B cell lymphomas in mice. Deregulation of Pim-2 expression has been documented in several human malignancies, including leukemia, lymphoma, multiple myeloma and prostate cancer. In human non-Hodgkin's lymphomas and in chronic lymphocytic leukemia Pim-2 is up-regulated and its expression correlates with disease activity. Pim-2 promotes cell survival in response to a wide variety of proliferative signals. Pim-2 promotes cell survival by phosphorylation of Bad and Cot. The goal of this study was to clarify the significance of our new unanticipated aspect of Pim-2′s function, namely, that over-expression of Pim-2 in HeLa cells led to cell cycle arrest at G1 and to increased apoptosis. We found that the G1 arrest was associated with increased (T14/Y15) phosphorylation of CDK2, increased proteosomic degradation of CDC25A, and increased levels of the CDK inhibitor p57. In addition, we found increased E2F-1 levels, which suggested the usage of the E2F-1 dependent apoptotic pathway. Using dominant negative forms of either E2F-1 or p73, which were co-expressed with Pim-2 in HeLa cells, revealed significant rescue of the G1 arrest and apoptotic phenomena. Silencing of Pim-2 in these cells, via siRNA, reversed the G1 arrest and pro-apoptotic effects, and verified the Pim-2 dependent specificity. We conclude that Pim-2 might play a dual role. Our data suggest that under certain environmental circumstances and in various cell types, Pim-2 appears to increase cell survival by abrogating some pro-apoptotic substrates, but under different proteomic associations Pim-2 might favor G1 arrest and apoptosis.
UR - https://scholar.google.co.il/scholar?q=Dual+role+of+Pim-2+depends+on+the+associated+proteome.+&btnG=&hl=en&as_sdt=0%2C5
M3 - Conference contribution
BT - N/A
ER -
