K63 Ubiquitination of P21 Can Facilitate Pellino-1 in the Context of Chronic Obstructive Pulmonary Disease and Lung Cellular Senescence

Autor: Jia-Hui Ma, Yi-Ting Zhang, Lu-Ping Wang, Qing-Yu Sun, Hao Zhang, Jian-Jiang Li, Ning-Ning Han, Yao-Yao Zhu, Xiao-Yu Xie, Xia Li
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cells, Vol 11, Iss 19, p 3115 (2022)
Druh dokumentu: article
ISSN: 11193115
2073-4409
62848046
DOI: 10.3390/cells11193115
Popis: Chronic obstructive pulmonary diseases (COPD) is a kind of age-related, airflow-obstruction disease mostly caused by cigarette smoke. However, the relationship between COPD and lung cellular senescence is still not fully understood. Here, we found silencing Pellino-1 could inhibit the protein level of P21. Then, through constructing cell lines expressed ubiquitin-HA, we found that the E3 ubiquitin ligase Pellino-1 could bind to senescence marker p21 and modify p21 by K63-site ubiquitination by co-IP assays. Furthermore, we found that p21-mediated lung cellular senescence could be inhibited by silencing Pellino-1 in a D-galactose senescence mice model. Moreover, by constructing a COPD mouse model with shPellino-1 adenovirus, we found that silencing Pellino-1 could inhibit COPD and inflammation via reduction of SASPs regulated by p21. Taken together, our study findings elucidated that silencing E3 ligase Pellino-1 exhibits therapeutic potential for treatment to attenuate the progression of lung cellular senescence and COPD.
Databáze: Directory of Open Access Journals
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