ArticleCell research2015
RHOBTB3 promotes proteasomal degradation of HIFα through facilitating hydroxylation and suppresses the Warburg effect.
Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Transcriptome analysis reveals the mechanism of Rhodiola polysaccharide affecting the proliferation of porcine Leydig cells under hypoxia.BMC veterinary research · 2025Article
- Article
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Characterization of tumour microenvironment reprogramming reveals invasion in epithelial ovarian carcinoma.Journal of ovarian research · 2023Article
- Screening and validating circular RNAs that estimate disease risk and treatment response of pediatric acute myeloid leukemia: a microarray-based analyses and RT-qPCR validation.Journal of cancer research and clinical oncology · 2023Article
- LINC02774 inhibits glycolysis in glioma to destabilize HIF-1α dependent on transcription factor RP58.MedComm · 2023Article
- Review
- Identifying a prognostic model and screening of potential natural compounds for acute myeloid leukemia.Translational cancer research · 2023Article
- RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1.Molecules and cells · 2022Article
- AMP-activated protein kinase α1 phosphorylates PHD2 to maintain systemic iron homeostasis.Clinical and translational medicine · 2022Article
- Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness.Molecular cancer · 2022Article
- Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes.Cell death & disease · 2021Article
- Construction of diagnostic and subtyping models for renal cell carcinoma by genome-wide DNA methylation profiles.Translational andrology and urology · 2021Article
- E3 ubiquitin ligases: styles, structures and functions.Molecular biomedicine · 2021Review
- Identification of RHOBTB2 aberration as an independent prognostic indicator in acute myeloid leukemia.Aging · 2021Article
- Article
- Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis.International journal of biological sciences · 2021Article
- Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma.Frontiers in oncology · 2021Article
- High Expression of RhoBTB3 Predicts Favorable Chemothrapy Outcomes in non-M3 Acute Myeloid Leukemia.Journal of Cancer · 2021Article
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factors (HIFs) are master regulators of adaptive responses to low oxygen, and their α-subunits are rapidly degraded through the ubiquitination-dependent proteasomal pathway after hydroxylation. Aberrant accumulation or activation of HIFs is closely linked to many types of cancer. However, how hydroxylation of HIFα and its delivery to the ubiquitination machinery are regulated remains unclear. Here we show that Rho-related BTB domain-containing protein 3 (RHOBTB3) directly interacts with the hydroxylase PHD2 to promote HIFα hydroxylation. RHOBTB3 also directly interacts with the von Hippel-Lindau (VHL) protein, a component of the E3 ubiquitin ligase complex, facilitating ubiquitination of HIFα. Remarkably, RHOBTB3 dimerizes with LIMD1, and constructs a RHOBTB3/LIMD1-PHD2-VHL-HIFα complex to effect the maximal degradation of HIFα. Hypoxia reduces the RHOBTB3-centered complex formation, resulting in an accumulation of HIFα. Importantly, the expression level of RHOBTB3 is greatly reduced in human renal carcinomas, and RHOBTB3 deficiency significantly elevates the Warburg effect and accelerates xenograft growth. Our work thus reveals that RHOBTB3 serves as a scaffold to organize a multi-subunit complex that promotes the hydroxylation, ubiquitination and degradation of HIFα.
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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.