2. Academic Validation
  3. KSHV transactivator-derived small peptide traps coactivators to attenuate MYC and inhibits leukemia and lymphoma cell growth

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

  • Commun Biol. 2021 Dec 2;4(1):1330. doi: 10.1038/s42003-021-02853-0.
Michiko Shimoda 1 2,  Yuanzhi Lyu 3,  Kang-Hsin Wang 3,  Ashish Kumar 3,  Hiroki Miura 3,  Joshua F Meckler 4 5,  Ryan R Davis 6,  Chanikarn Chantarasrivong 7,  Chie Izumiya 3,  Clifford G Tepper 4 8,  Ken-Ichi Nakajima 3,  Joseph Tuscano 4 5,  Gustavo Barisone 4 5,  Yoshihiro Izumiya 9 10 11
Affiliations

Affiliations

  • 1 Department of Dermatology, School of Medicine, University of California Davis (UC Davis), Sacramento, CA, USA. mshimoda@ucdavis.edu.
  • 2 UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. mshimoda@ucdavis.edu.
  • 3 Department of Dermatology, School of Medicine, University of California Davis (UC Davis), Sacramento, CA, USA.
  • 4 UC Davis Comprehensive Cancer Center, Sacramento, CA, USA.
  • 5 Department of Internal Medicine, School of Medicine, UC Davis, Sacramento, CA, USA.
  • 6 Department of Pathology and Laboratory Medicine, School of Medicine, UC Davis, Sacramento, CA, USA.
  • 7 Lifematics Inc., Osaka, Japan.
  • 8 Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, Sacramento, CA, USA.
  • 9 Department of Dermatology, School of Medicine, University of California Davis (UC Davis), Sacramento, CA, USA. yizumiya@ucdavis.edu.
  • 10 UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. yizumiya@ucdavis.edu.
  • 11 Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, Sacramento, CA, USA. yizumiya@ucdavis.edu.
PMID: 34857874 DOI: 10.1038/s42003-021-02853-0
Abstract

In herpesvirus replicating cells, host cell gene transcription is frequently down-regulated because important transcriptional apparatuses are appropriated by viral transcription factors. Here, we show a small peptide derived from the Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta) sequence, which attenuates cellular MYC expression, reduces cell proliferation, and selectively kills Cancer cell lines in both tissue culture and a xenograft tumor mouse model. Mechanistically, the peptide functions as a decoy to block the recruitment of coactivator complexes consisting of Nuclear receptor coactivator 2 (NCOA2), p300, and SWI/SNF proteins to the MYC promoter in primary effusion lymphoma cells. Thiol(SH)-linked alkylation for the metabolic Sequencing of RNA (SLAM seq) with target-transcriptional analyses further confirm that the viral peptide directly attenuates MYC and MYC-target gene expression. This study thus provides a unique tool to control MYC activation, which may be used as a therapeutic payload to treat MYC-dependent diseases such as cancers and autoimmune diseases.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P10418
    抗肿瘤剂
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