ArticleOncogene2021
A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- The RPS15-DDX21 complex drives prostate malignancy through transcriptional activation of SCD1.Oncogene · 2026Article
- Biochemical and Comparative Proteomic Analyses Delineate the Anti-Ovarian Carcinogenic Roles of Modified Calycosin.Food science & nutrition · 2026Article
- USP1-TRAF2 axis-regulated mortalin stability mediates chemoresistance by disrupting calcium transport in peripheral T-cell lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- AKAP1/PKA-mediated GRP75 phosphorylation at mitochondria-associated endoplasmic reticulum membranes protects cancer cells against ferroptosis.Cell death and differentiation · 2025Article
- The other side of the coin: protein deubiquitination by Ubiquitin-Specific Protease 1 in cancer progression and therapy.Future medicinal chemistry · 2025Review
- The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.Oncogene · 2025Article
- Identification of biomarkers based on ubiquitin-correlated genes for predicting immune profile and drug sensitivity in lung adenocarcinoma.Frontiers in pharmacology · 2025Article
- SENP3 mediates deSUMOylation of SIX1 to promote prostate cancer proliferation and migration.Cellular & molecular biology letters · 2024Article
- Implications of ITCH-mediated ubiquitination of SIX1 on CDC27-cyclinB1 signaling in nasopharyngeal carcinoma.Scientific reports · 2024Article
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
- Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Roles of USP1 in Ewing sarcoma.Genes & cancer · 2024Article
- Ubiquitin-specific peptidase 1: assessing its role in cancer therapy.Clinical and experimental medicine · 2023Review
- HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Nuclear transport maintenance of USP22-AR by Importin-7 promotes breast cancer progression.Cell death discovery · 2023Article
- SNS-023 sensitizes hepatocellular carcinoma to sorafenib by inducing degradation of cancer drivers SIX1 and RPS16.Acta pharmacologica Sinica · 2023Article
- Retinal determination gene networks: from biological functions to therapeutic strategies.Biomarker research · 2023Review
- Review
- Neddylation of HER2 Inhibits its Protein Degradation and promotes Breast Cancer Progression.International journal of biological sciences · 2023Article
Corrections and comments
- Commented on byUro-Science.2022
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancer (PC) is the second most common cancer with limited treatment option in males. Although the reactivation of embryonic signals in adult cells is one of the characteristics of cancer, the underlying protein degradation mechanism remains elusive. Here, we show that the molecular chaperone GRP75 is a key player in PC cells by maintaining the protein stability of SIX1, a transcription factor for embryonic development. Mechanistically, GRP75 provides a platform to recruit the deubiquitinating enzyme USP1 to inhibit K48-linked polyubiquitination of SIX1. Structurally, the C-terminus of GRP75 (433-679 aa) contains a peptide binding domain, which is required for the formation of GRP75-USP1-SIX1 protein complex. Functionally, pharmacological or genetic inhibition of the GRP75-USP1-SIX1 protein complex suppresses tumor growth and overcomes the castration resistance of PC cells in vitro and in xenograft mouse models. Clinically, the protein expression of SIX1 in PC tumor tissues is positively correlated with the expression of GRP75 and USP1. These new findings not only enhance our understanding of the protein degradation mechanism, but also may provide a potential way to enhance the anti-cancer activity of androgen suppression therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.