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Nat. Commun., Feb 01 2025, 16 (1) | https://doi.org/10.1038/s41467-025-56440-6
The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development
Soeun Hwang1, Junhee Park1, Seo-Young Koo1, Si-Yeon Lee1, Yunju Jo2, Dongryeol Ryu2, Heounjeong Go3 & Chang-Woo Lee1,4
1Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea.
2Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, South Korea.
3Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
4Research Institute, Curogen Technology, Suwon 16419, South Korea.
Corresponding author
Correspondence to Chang-Woo Lee.
1Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea.
2Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, South Korea.
3Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
4Research Institute, Curogen Technology, Suwon 16419, South Korea.
Corresponding author
Correspondence to Chang-Woo Lee.
Abstract
Receptor-mediated signaling could be modulated by ubiquitination of pathway intermediates, but the role of such modification in the pathogenesis of inflammation and inflammation-related cancer is lesser known. The ubiquitin ligase Pellino1 has been shown to modulate immune signals by enabling various immune cells to respond to their receptor signals effectively. Here, we show that Pellino1 levels are elevated in patients with colitis, patients with colitis-associated colon cancer (CAC), and murine models of these conditions. In a monocyte-specific Pellino1 knock-out mouse model, we find reduced macrophage migration and activation, leading to attenuated development of colitis and CAC in male mice. Mechanistically, Pellino1 targets STAT3 for lysine 63-mediated ubiquitination, resulting in pathogenic activation of STAT3 signaling. Taken together, our findings reveal a macrophage-specific ubiquitination signaling axis in colitis and CAC development and suggest that Pellino1 is a potential candidate for treating chronic inflammation and inflammation-related cancer.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-03)
- 국내 연구진
- 생명과학 > 유전자발현
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