1. ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival.
- Author
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Van Hook, Kathryn, Wang, Zhiping, Chen, Dexi, Nold, Casey, Zhu, Zhiyi, Anur, Pavana, Lee, Hun-Joo, Yu, Zhiyong, Sheppard, Brett, Dai, Mu-Shui, Sears, Rosalie, Spellman, Paul, and Lopez, Charles D.
- Subjects
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TUMOR suppressor proteins , *GENETIC transcription , *GENETIC toxicology , *BREAST tumors , *APOPTOSIS , *GENE expression - Abstract
ASPP2 is a tumor suppressor that works, at least in part, through enhancing p53-dependent apoptosis. We now describe a new ASPP2 isoform, ΔN-ASPP2, generated from an internal transcription start site that encodes an N-terminally truncated protein missing a predicted 254 amino acids. ΔN-ASPP2 suppresses p53 target gene transactivation, promoter occupancy, and endogenous p53 target gene expression in response to DNA damage. Moreover, ΔN-ASPP2 promotes progression through the cell cycle, as well as resistance to genotoxic stress-induced growth inhibition and apoptosis. Additionally, we found that ΔN-ASPP2 expression is increased in human breast tumors as compared to adjacent normal breast tissue; in contrast, ASPP2 is suppressed in the majority of these breast tumors. Together, our results provide insight into how this new ASPP2 isoform may play a role in regulating the ASPP2-p53 axis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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