| First Author | Hammerman PS | Year | 2004 |
| Journal | Cancer Res | Volume | 64 |
| Issue | 22 | Pages | 8341-8 |
| PubMed ID | 15548703 | Mgi Jnum | J:93995 |
| Mgi Id | MGI:3510500 | Doi | 10.1158/0008-5472.CAN-04-2284 |
| Citation | Hammerman PS, et al. (2004) Lymphocyte transformation by Pim-2 is dependent on nuclear factor-kappaB activation. Cancer Res 64(22):8341-8 |
| abstractText | Pim-2 is a transcriptionally regulated oncogenic kinase that promotes cell survival in response to a wide variety of proliferative signals. Deregulation of Pim-2 expression has been documented in several human malignancies, including leukemia, lymphoma, and multiple myeloma. Here, we show that the ability of Pim-2 to promote survival of cells is dependent on nuclear factor (NF)-kappaB activation. Pim-2 activates NF-kappaB-dependent gene expression by inducing phosphorylation of the oncogenic serine/threonine kinase Cot, leading to both augmentation of IkappaB kinase activity and a shift in nuclear NF-kappaB from predominantly p50 homodimers to p50/p65 heterodimers. Blockade of NF-kappaB function eliminates Pim-2-mediated survival in both cell lines and primary cells, and both Cot phosphorylation and expression are required for the prosurvival effects of Pim-2. Although Pim-2 cooperates with Myc to promote growth factor-independent cell proliferation, this feature is abrogated by NF-kappaB blockade. The ability of Pim-2 to serve as an oncogene in vivo depends on sustained NF-kappaB activity. Thus, the transcriptional induction of Pim-2 initiates a novel NF-kappaB activation pathway that regulates cell survival. |
