ArticleThe Journal of biological chemistry2018
Sal-like 4 protein levels in breast cancer cells are post-translationally down-regulated by tripartite motif-containing 21.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- TRIM21-Mediated ubiquitination of FBL suppresses PI3K/AKT signaling and tumor progression in clear cell renal cell carcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- MiR-99a-3p downregulates TRIM21 to promote gastric cancer development.Molecular and cellular biochemistry · 2025Article
- [TRIM21 Inhibits the Proliferation and Migration of Lung Adenocarcinoma Cells by Interacting with ZSWIM1].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- The interconnected roles of TRIM21/Ro52 in systemic lupus erythematosus, primary Sjögren's syndrome, cancers, and cancer metabolism.Cancer cell international · 2023Review
- The new advance of SALL4 in cancer: Function, regulation, and implication.Journal of clinical laboratory analysis · 2023Review
- Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity.Science advances · 2023Article
- CDK7/GRP78 signaling axis contributes to tumor growth and metastasis in osteosarcoma.Oncogene · 2022Article
- TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination.Nucleic acids research · 2022Article
- SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance.International journal of molecular sciences · 2022Review
- The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment.Frontiers in immunology · 2022Review
- Anesthetic Propofol Promotes Tumor Metastasis in Lungs via GABAAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Overexpression of Sal-like protein 4 in head and neck cancer: epigenetic effects and clinical correlations.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer.Frontiers in oncology · 2020Article
- Spalt-like transcription factor 4 expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical appraisal.Journal of carcinogenesis · 2020Article
- Decreased expression of TRIM21 indicates unfavorable outcome and promotes cell growth in breast cancer.Cancer management and research · 2018Article
- Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels.The Journal of biological chemistryArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sal-like 4 (SALL4) is a transcription factor that enhances proliferation and migration in breast cancer cells. SALL4 expression therefore has the potential to promote cancer malignancy. However, the regulatory mechanisms involved in SALL4 protein expression have not been thoroughly elucidated. In this study, we observed that treating MCF-7 and SUM159 breast cancer cell lines with a proteasome inhibitor increases SALL4 protein levels, suggesting that SALL4 is degraded by the ubiquitin-proteasome system. Using immunoprecipitation to uncover SALL4-binding proteins, we identified an E3 ubiquitin-protein ligase, tripartite motif-containing 21 (TRIM21). Using an EGFP reporter probe of the major SALL4 isoform SALL4B, we observed that shRNA-mediated knockdown of TRIM21 increases cellular SALL4B levels. Immunostaining experiments revealed that TRIM21 localizes to the nucleus, and a K64R substitution in the nuclear localization motif in SALL4B increased SALL4B levels in the cytoplasm. These results suggested that TRIM21 is involved in nuclear SALL4 degradation. To identify the amino acid residue that is targeted by TRIM21, we fragmented the SALL4B sequence, fused it to EGFP, and identified Lys-190 in SALL4B as TRIM21's target residue. Amino acid sequence alignments of SALL family members indicated that the region around SALL4 Lys-190 is conserved in both SALL1 and SALL3. Because SALL1 and SALL4 have similar functions, we constructed a SALL1-EGFP probe and found that the TRIM21 knockdown increases SALL1 levels, indicating that TRIM21 degrades both SALL1 and SALL4. Our findings extend our understanding of SALL4 and SALL1 regulation and may contribute to the development of SALL4-targeting therapies.
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