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

Journal Article · Sun Jan 22 04:00:00 EST 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2016.12.027· OSTI ID:22696803

Van Hook, Kathryn; Wang, Zhiping ^[1]; Chen, Dexi ^[1]; Nold, Casey; Zhu, Zhiyi ^[1]; Anur, Pavana ^[2]; Lee, Hun-Joo ^[1]; Yu, Zhiyong ^[3]; Sheppard, Brett ^[4]; Dai, Mu-Shui; Sears, Rosalie; Spellman, Paul ^[2]

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1. Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239 (United States)
2. Department of Molecular and Medical Genetics and the Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239 (United States)
3. Shandong Tumor Hospital and Institute, Jinan, 250117 (China)
4. Department of Surgery and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239 (United States)

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. - Highlights: • ΔN-ASPP2 is a N-terminal truncated ASPP2 isoform. • ΔN-ASPP2 antagonizes p53 transactivation and p53 promoter occupancy after cellular stress. • ΔN-ASPP2 promotes cell proliferation and suppresses cytotoxic damage-induced growth inhibition and apoptosis. • ΔN-ASPP2 is overexpressed in human breast tumors compared to adjacent normal breast tissue.

• OSTI ID: 22696803
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 482; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
APOPTOSIS
CELL CYCLE
CELL PROLIFERATION
DNA DAMAGES
INHIBITION
MAMMARY GLANDS
NEOPLASMS
PLANT GROWTH
TUMOR PROMOTERS