Disease relevance of Pim1

• Pim-1 was substantially induced in neointimal VSMCs of balloon-injured rat carotid arteries, and in vivo infection with a dominant negative Pim-1-expressing adenovirus (Ad-DN-Pim-1) markedly suppressed neointima formation and cell cycle progression in the balloon-injured arteries [1].
• Here, we demonstrate that NFATc-dependent transcription is inducible also in NGF-differentiated rat PC12 pheochromocytoma cells treated with phorbol esthers, calcium ionophores and/or forskolin and that the Pim-1 kinase can further potentiate the effects of these agents [2].

High impact information on Pim1

• In cultured VSMCs, treatment with serum or H(2)O(2) induced Pim-1 expression, and H(2)O(2)- or serum-stimulated cell cycle progression and DNA synthesis were almost completely inhibited by DN-Pim-1 overexpression [1].
• Furthermore, we performed immunohisto-chemical staining for Pim-1 in human thoracic aortas and coronary arteries obtained from six individuals at autopsy and found that Pim-1-positive cells are observed predominantly in the thickened intima of the aortas and coronary arteries [1].
• Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway [3].
• In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis [3].
• We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity [3].

Anatomical context of Pim1

• In this study, therefore, we examined the effect of Pim-1 expression on c-Myc-mediated apoptosis of Rat-1 fibroblasts triggered by serum deprivation [4].
• mRNA expression of the serine/threonine kinase protooncogene Pim-1 was investigated in mitogen-treated normal bovine lymphocytes [5].
• Pim-1 kinase enhances NFATc activity and neuroendocrine functions in PC12 cells [2].
• The activity of NFATc family transcription factors is tightly regulated in T cells via signaling pathways initiated by stimulation of the T cell receptor or its downstream effectors such as the Pim-1 serine/threonine kinase [2].

Associations of Pim1 with chemical compounds

• Together, these results suggest that Pim-1 oncoprotein stimulates as a serine/threonine kinase the death signaling elicited by c-Myc at a step upstream of caspase-3-like protease activation in Rat-1 fibroblasts [4].

Regulatory relationships of Pim1

• Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation [4].

Other interactions of Pim1

• Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis, but also in apoptosis induction [3].
• Although the molecular mechanism of this cooperative transformation remains unknown, it is speculated that, similar to Bcl-2, Pim-1 contributes to transformation by inhibiting apoptosis [4].

References