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

Kathryn Van Hook1, Zhiping Wang1, Dexi Chen2

  • 1Department of Medicine, Division of Hematology and Medical Oncology and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.

Biochemical and Biophysical Research Communications
|December 13, 2016
PubMed

Insights

A newly discovered ASPP2 protein isoform, ΔN-ASPP2, promotes cancer progression by suppressing tumor suppressor p53 activity and increasing resistance to DNA damage, contrasting with the known tumor-suppressing ASPP2 protein.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The tumor suppressor ASPP2 (Apoptosis-Stimulating Protein of p53) plays a crucial role in cancer by promoting p53-dependent apoptosis.
  • Understanding the regulation of ASPP2 is vital for cancer therapy.

Purpose of the Study:

  • To characterize a novel ASPP2 isoform, ΔN-ASPP2, and elucidate its role in cancer progression and the ASPP2-p53 axis.
  • To investigate the expression patterns of ΔN-ASPP2 and ASPP2 in human breast tumors.

Main Methods:

  • Identification and characterization of the ΔN-ASPP2 isoform.
  • Assays to evaluate the impact of ΔN-ASPP2 on p53 target gene transactivation and expression.
  • Cell cycle progression and apoptosis assays under genotoxic stress.
  • Quantitative analysis of ASPP2 and ΔN-ASPP2 expression in breast tumor tissues.

Main Results:

  • A new isoform, ΔN-ASPP2, was identified, lacking the N-terminal 254 amino acids of ASPP2.
  • ΔN-ASPP2 suppresses p53-mediated transactivation, promoter binding, and gene expression following DNA damage.
  • ΔN-ASPP2 enhances cell cycle progression and confers resistance to genotoxic stress-induced apoptosis and growth inhibition.
  • ΔN-ASPP2 expression is elevated in human breast tumors, while full-length ASPP2 is suppressed.

Conclusions:

  • The ΔN-ASPP2 isoform acts as a functional antagonist to ASPP2, promoting cell cycle progression and survival under stress.
  • Increased ΔN-ASPP2 expression in breast tumors suggests its contribution to tumorigenesis by counteracting ASPP2's tumor-suppressive functions.
  • This discovery reveals a new regulatory mechanism within the ASPP2-p53 pathway with potential implications for cancer diagnostics and therapeutics.
Keywords:
ASPP2Tumor suppressorp53

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