ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival

Kathryn Van Hook, Zhiping Wang, Dexi Chen, Casey Nold, Zhiyi Zhu, Pavana Anur, Hun Joo Lee, Zhiyong Yu, Brett Sheppard, Mu Shui Dai, Rosalie Sears, Paul Spellman, Charles D. Lopez

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1271-1277
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume482
Issue number4
DOIs
StatePublished - Jan 22 2017

Keywords

  • ASPP2
  • Tumor suppressor
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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