KSHV transactivator-derived small peptide traps coactivators to attenuate MYC and inhibits leukemia and lymphoma cell

Michiko Shimoda1,2, Yuanzhi Lyu3, Kang-Hsin Wang3

  • 1Department of Dermatology, School of Medicine, University of California Davis (UC Davis), Sacramento, CA, USA. mshimoda@ucdavis.edu.

Communications Biology
|December 3, 2021
PubMed

Insights

A novel peptide from a herpesvirus protein selectively kills cancer cells by blocking MYC gene activation. This discovery offers a potential new therapy for MYC-dependent cancers and autoimmune diseases.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Herpesvirus replication often suppresses host cell gene transcription by viral factors hijacking cellular machinery.
  • The MYC gene is a critical regulator of cell proliferation and is frequently dysregulated in various cancers.

Purpose of the Study:

  • To investigate a novel peptide derived from Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta) as a potential therapeutic agent.
  • To determine the mechanism by which this peptide affects MYC expression and cancer cell viability.

Main Methods:

  • A synthetic peptide based on K-Rta was designed and tested in cancer cell lines and a xenograft mouse model.
  • Mechanistic studies involved assessing coactivator complex recruitment to the MYC promoter using techniques like SLAM seq and transcriptional analyses.

Main Results:

  • The K-Rta-derived peptide effectively reduced MYC expression and cell proliferation in cancer cell lines.
  • The peptide selectively induced cancer cell death in vitro and in vivo.
  • Mechanistically, the peptide acted as a decoy, preventing the assembly of essential coactivator complexes (NCOA2, p300, SWI/SNF) at the MYC promoter.

Conclusions:

  • A K-Rta-derived peptide serves as a potent inhibitor of MYC transcription and a selective cancer cell killer.
  • This peptide represents a promising therapeutic strategy for diseases driven by MYC activation, including cancers and autoimmune disorders.

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