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Peer-reviewedCC BY 4.0Experimental & Molecular Medicine

KSHV vIRF3–PKM2 interaction induces SMAD5 acetylation, promoting Kaposi’s sarcoma progression

  • Yeong Jun Kim1
  • Juhyeon Lim2
  • Jae Jin Lee2
  • Abhishek Kumar3
  • Shrute Kannappan4
  • Junjie Zhang5
  • Soochi Kim1
  • Han-Jun Kim6
  • Kyeong Kyu Kim4
  • Zsolt Toth3
  • Hyungjin Eoh2,7
  • Kyung-Chul Choi8
1 more authors
  • Hye-Ra Lee1,9
9 affiliations
  1. 1Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong, Republic of Korea
  2. 2Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA USA
  3. 3Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL USA
  4. 4Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
  5. 5The State Key Laboratory of Virology, Medical Research Institute, Wuhan University, Wuhan, China
  6. 6College of Pharmacy, Korea University, Sejong, Republic of Korea
  7. 7Department of Ophthalmology, University of Southern California, Los Angeles, CA USA
  8. 8Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea
  9. 9Department of Lab Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
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Abstract

Kaposi’s sarcoma (KS), induced by Kaposi’s sarcoma-associated herpesvirus (KSHV), is a multicentric tumor of lymphatic endothelial origin. However, the fundamental molecular mechanisms underlying the KS progression remain poorly understood. Here we found that interaction between KSHV vIRF3 and PKM2 controls the metabolic switch of lymphatic endothelial cells (LECs), inducing disseminated visceral KS in xenograft models of KSHV-infected LECs. Mechanistically, vIRF3–PKM2 interaction elevates intracellular acetyl coenzyme A (acetyl-CoA) level by augmenting the PKM2 enzymatic activity, leading to SMAD5 acetylation, which contributes to the endothelia-to-mesenchymal transition of LECs. Notably, a vIRF3-derived short peptide acts as a potent and selective PKM2 antagonist, effectively regressing KS progression. Collectively, these results suggest that vIRF3 plays a pivotal role in KS malignancy by linking acetyl-CoA metabolic reprogramming to cancer progression.

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Cite

BibTeXRIS
BibTeX
@article{kim2026kshv,
  title = {{KSHV vIRF3–PKM2 interaction induces SMAD5 acetylation, promoting Kaposi’s sarcoma progression}},
  author = {Yeong Jun Kim and Juhyeon Lim and Jae Jin Lee and Abhishek Kumar and Shrute Kannappan and Junjie Zhang and Soochi Kim and Han-Jun Kim and Kyeong Kyu Kim and Zsolt Toth and Hyungjin Eoh and Kyung-Chul Choi and Hye-Ra Lee},
  journal = {Experimental \& Molecular Medicine},
  year = {2026},
  month = oct,
  doi = {10.1038/s12276-026-01849-2},
  url = {https://doi.org/10.1038/s12276-026-01849-2},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - KSHV vIRF3–PKM2 interaction induces SMAD5 acetylation, promoting Kaposi’s sarcoma progression
AU  - Yeong Jun Kim
AU  - Juhyeon Lim
AU  - Jae Jin Lee
AU  - Abhishek Kumar
AU  - Shrute Kannappan
AU  - Junjie Zhang
AU  - Soochi Kim
AU  - Han-Jun Kim
AU  - Kyeong Kyu Kim
AU  - Zsolt Toth
AU  - Hyungjin Eoh
AU  - Kyung-Chul Choi
AU  - Hye-Ra Lee
PY  - 2026
DA  - 2026/10/05
JO  - Experimental & Molecular Medicine
DO  - 10.1038/s12276-026-01849-2
UR  - https://doi.org/10.1038/s12276-026-01849-2
AB  - Kaposi’s sarcoma (KS), induced by Kaposi’s sarcoma-associated herpesvirus (KSHV), is a multicentric tumor of lymphatic endothelial origin. However, the fundamental molecular mechanisms underlying the KS progression remain poorly understood. Here we found that interaction between KSHV vIRF3 and PKM2 controls the metabolic switch of lymphatic endothelial cells (LECs), inducing disseminated visceral KS in xenograft models of KSHV-infected LECs. Mechanistically, vIRF3–PKM2 interaction elevates intracellular acetyl coenzyme A (acetyl-CoA) level by augmenting the PKM2 enzymatic activity, leading to SMAD5 acetylation, which contributes to the endothelia-to-mesenchymal transition of LECs. Notably, a vIRF3-derived short peptide acts as a potent and selective PKM2 antagonist, effectively regressing KS progression. Collectively, these results suggest that vIRF3 plays a pivotal role in KS malignancy by linking acetyl-CoA metabolic reprogramming to cancer progression.
SN  - 1226-3613
SN  - 2092-6413
ER  -