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A positive feedback loop between Pim-1 kinase and HBP1 transcription factor contributes to hydrogen peroxide-induced premature senescence and apoptosis.
- Source :
-
Journal of Biological Chemistry . 5/19/2017, Vol. 292 Issue 20, p8207-8222. 16p. - Publication Year :
- 2017
-
Abstract
- Oxidative stress can induce cell dysfunction and lead to a broad range of degenerative alterations, including carcinogenesis, aging, and other oxidative stress-related conditions. To avoid undergoing carcinogenesis in response to oxidative stress, cells trigger a succession of checkpoint responses, including premature senescence and apoptosis. Increasing evidence indicates that H2O2, an important cause of oxidative stress, functions as an important physiological regulator of intracellular signaling pathways that participate in regulation of cell premature senescence and apoptosis. However, the precise mechanisms underlying this process remain to be studied extensively. In this study, we describe the importance of Pim-1 kinase in this checkpointresponsetooxidativestress.Pim-1bindstoandphosphorylates the transcription factor high mobility group box transcription factor 1 (HBP1), activating it. H2O2 enhances the interaction between Pim-1 and HBP1 and promotes HBP1 accumulation. In turn, HBP1 rapidly and selectively up-regulates Pim-1 expression in H2O2-stimulated cells, thereby creating a Pim-1-HBP1 positive feedback loop that regulates H2O2-induced premature senescence and apoptosis. Furthermore, the Pim-1-HBP1 positive feedback loop exerts its effect by regulating the senescence markers DNMT1 and p16 and the apoptosis marker Bax. The Pim-1-HBP1 axis thus constitutes a novel checkpoint pathway critical for the inhibition of tumorigenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *APOPTOSIS
*CELLULAR aging
*PROTEIN kinases
*OXIDATIVE stress
*HYDROGEN peroxide
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 292
- Issue :
- 20
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 123176462
- Full Text :
- https://doi.org/10.1074/jbc.M116.768101