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Review
. 2025 Jul 15:13:1637451.
doi: 10.3389/fcell.2025.1637451. eCollection 2025.

TRIM21: a multifaceted regulator in cancer

Aizhuo Li #  1 , Jiannan Wang #  1 , Yi Qu  2
Affiliations
Review

TRIM21: a multifaceted regulator in cancer

Aizhuo Li et al. Front Cell Dev Biol. .

Abstract

Ubiquitination serves as a dynamic post-translational modification that enables rapid and precise regulation of cellular signaling networks. TRIM21, as an important member of the TRIM family, is a protein with E3 ubiquitin ligase activity. By specifically recognizing and ubiquitinating various substrate proteins, it plays a pivotal regulatory role in tumorigenesis and development. Moreover, TRIM21 has been found to play a multi-faceted role in cellular autophagy, metabolic reprogramming, immune escape, tumor proliferation, metastasis and resistance to cell death by regulating the stability and function of key proteins. In this review, we provided an in-depth understanding of the specific mechanism of TRIM21 in different biological processes and tumor types, which contributes to the development of novel targeted therapeutic strategies targeting TRIM21.

Keywords: autophagy; cancer; immunity; metabolism; ubiquination.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The domains of tripartite motif 21 (TRIM21) protein.
FIGURE 2
FIGURE 2
Substrates of tripartite motif 21 (TRIM21) in cellular autophagy. Abbreviations: ER, endoplasmic reticulum; IFRD1, interferon-related developmental regulator 1; LIR, LC3-interacting region; RETREG1, reticulophagy regulator 1.
FIGURE 3
FIGURE 3
Substrates of tripartite motif 21 (TRIM21) in cellular metabolism. Abbreviations: ACLY, ATP citrate lyase; FASN, Fatty acid synthase; HK2, Hexokinase 2; G6PD, Glucose-6-phosphate dehydrogenase; PFK, Phosphofructokinase; SREBF-1, Sterol regulatory element-binding protein gene.
See this image and copyright information in PMC

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