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ASPP and iASPP: Implication in cancer development and progression.

Y Li1, A Ahmad1, F H Sarkar2

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Cellular and Molecular Biology (Noisy-Le-Grand, France)
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The apoptosis stimulating proteins of p53 (ASPP) family regulates apoptosis. Targeting ASPP family proteins, like ASPP1, ASPP2, and iASPP, shows promise in inducing cancer cell apoptosis and improving drug sensitivity.

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Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Death Pathways

Background:

  • The tumor suppressor protein p53 is crucial for apoptosis induction following DNA damage.
  • Mutant p53 impairs apoptosis, contributing to cancer progression and drug resistance.
  • The apoptosis stimulating proteins of p53 (ASPP) family, including tumor suppressors ASPP1/ASPP2 and oncogenic iASPP, modulate p53 activity and apoptosis.

Purpose of the Study:

  • To elucidate the role of the ASPP family in cancer and apoptosis.
  • To explore the therapeutic potential of targeting the ASPP family in cancer treatment.

Main Methods:

  • Analysis of aberrant expression of ASPP family members in cancer cells.
  • Investigation of molecular interactions within the ASPP-mediated apoptotic signaling network.
  • Review of therapeutic strategies targeting the ASPP family.

Main Results:

  • Aberrant expression of ASPP1, ASPP2, and iASPP is observed in cancers, with high iASPP correlating with poor prognosis and therapy resistance.
  • ASPP1 and ASPP2 promote apoptosis by interacting with proteins like p53, p63, p73, and Bcl-2.
  • iASPP overexpression inhibits DNA damage-induced apoptosis.
  • Complex signaling networks involving ASPP family members, miRNAs, and transcription factors regulate apoptosis and tumor growth.

Conclusions:

  • Targeting the ASPP family offers a potential strategy to restore apoptosis and enhance drug sensitivity in cancer.
  • Peptides, miRNAs, and natural agents targeting the ASPP family have shown preliminary success in inducing cancer cell apoptosis.
  • Further in vivo and clinical studies are necessary to validate the therapeutic efficacy of targeting the ASPP family for cancer treatment.