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TRIP13 - a potential drug target in cancer pharmacotherapy

Samuel Jacob Bunu1, Haiyan Cai2, Leyun Wu1

  • 1State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China.

Bioorganic Chemistry
|July 23, 2024
PubMed

Insights

Thyroid Hormone Receptor Interacting Protein-13 (TRIP13) is an AAA+ ATPase and oncogene. This review details TRIP13

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Oncology

Background:

  • ATPases Associated with Diverse Cellular Activity (AAA+ATPases) are crucial enzymatic proteins in human cells.
  • Thyroid Hormone Receptor Interacting Protein-13 (TRIP13) is an AAA+ ATPase implicated in DNA repair and mitosis.
  • TRIP13 functions as an oncogene in various human malignancies, including brain tumors and multiple myeloma.

Purpose of the Study:

  • To provide a comprehensive review of TRIP13's biological functions, structure, and role in cancer.
  • To explore the molecular mechanisms underlying TRIP13's activity and its interactions, such as with MAD2.
  • To discuss the potential of TRIP13 as an anticancer drug target, including known small-molecule inhibitors.

Main Methods:

  • Systematic review of existing literature on TRIP13.
  • Analysis of TRIP13's protein structure and ATP binding mechanisms.
  • Compilation of data on TRIP13's involvement in eighteen different cancer types.

Main Results:

  • TRIP13's structure elucidates its ATP binding and MAD2 recognition mechanisms, with p31comet as an adapter.
  • TRIP13 is implicated in the progression of at least eighteen human cancers.
  • Four small-molecule inhibitors (DCZ0415, TI17, DCZ5417, DCZ5418) demonstrate significant inhibition of TRIP13 and suppression of cancer cells.

Conclusions:

  • TRIP13 is a validated and significant anticancer drug target due to its oncogenic functions.
  • Small-molecule inhibitors targeting TRIP13 show promise for cancer therapy.
  • Further research into TRIP13's mechanisms and inhibitors could lead to novel therapeutic strategies.
Keywords:
AAA(+) ATPaseCancerDrug targetSmall-molecule inhibitorsTRIP13

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