Sequential ubiquitination of p53 by TRIM28, RLIM, and MDM2 in lung tumorigenesis.

Jun-O Jin, Geun Dong Lee, Sang Hee Nam, Tae Hyeong Lee, Dong Hoon Kang, Jae Kwang Yun, Peter Chang-Whan Lee

Cell death and differentiation 2021 Jun

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Tripartite motif-containing 28 (TRIM28) is an E3 ubiquitin ligase harboring multiple cellular functions. We found that the TRIM28 protein is frequently overexpressed in patients with lung cancer. The stable overexpression of TRIM28 in lung cancer cells and xenograft models significantly increased the proliferation, migration, and invasiveness, whereas knockdown of TRIM28 had the opposite effect. We further observed that TRIM28 regulates the ubiquitin ligases RLIM and MDM2 to target the p53 levels during lung tumorigenesis. These data provide new insights into lung cancer development and potential new therapeutic targets for this disease.

Citation

Jun-O Jin, Geun Dong Lee, Sang Hee Nam, Tae Hyeong Lee, Dong Hoon Kang, Jae Kwang Yun, Peter Chang-Whan Lee. Sequential ubiquitination of p53 by TRIM28, RLIM, and MDM2 in lung tumorigenesis. Cell death and differentiation. 2021 Jun;28(6):1790-1803