ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Rapid generation of a sdhb loss-of-function zebrafish model for secreting pheochromocytomas and paragangliomas.NPJ genomic medicine · 2025Article
- SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis.Frontiers in endocrinology · 2023Article
- Genetic impairment of succinate metabolism disrupts bioenergetic sensing in adrenal neuroendocrine cancer.Cell reports · 2022Article
- Papillary Thyroid Cancer and aJournal of the Endocrine Society · 2022Article
- Review
- Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation.Science immunology · 2022Article
- Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas.Oncology research · 2022Review
- High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.Translational oncology · 2021Article
- Single nucleotide variants of succinate dehydrogenase A gene in renal cell carcinoma.Cancer science · 2021Article
- Differential expression of skeletal muscle mitochondrial proteins in yak, dzo, and cattle: a proteomics-based study.The Journal of veterinary medical science · 2020Article
- Article
- Review
- Bortezomib Alone and in Combination With Salinosporamid A Induces Apoptosis and Promotes Pheochromocytoma Cell Death In Vitro and in Female Nude Mice.Endocrinology · 2017Article
- Altered expression of Tumor Necrosis Factor Alpha -Induced Protein 3 correlates with disease severity in Ulcerative Colitis.Scientific reports · 2017Article
- Implications of SDHB genetic testing in patients with sporadic pheochromocytoma.Langenbeck's archives of surgery · 2017Article
- A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III.Cell metabolism · 2017Article
- Pheochromocytoma: The First Metabolic Endocrine Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- Pheochromocytoma: Gasping for Air.Hormones & cancer · 2015Review
- Instability of succinate dehydrogenase in SDHD polymorphism connects reactive oxygen species production to nuclear and mitochondrial genomic mutations in yeast.Antioxidants & redox signaling · 2015Article
- Mutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90 chaperone complex for proteasomal degradation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations of succinate dehydrogenase subunit B (SDHB) play a crucial role in the pathogenesis of the most aggressive and metastatic pheochromocytomas (PHEOs) and paragangliomas (PGLs). Although a variety of missense mutations in the coding sequence of the SDHB gene have been found in PHEOs and PGLs, it has been unclear whether these mutations impair mRNA expression, protein stability, subcellular localization, or intrinsic protein function. RT-PCR and Western blot analysis of SDHB mRNA and protein expression from SDHB-related PHEOs and PGLs demonstrated intact mRNA expression but significantly reduced protein expression compared to non-SDHB PHEOs and PGLs. A pulse-chase assay of common SDHB missense mutations in transfected HeLa cell lines demonstrated that the loss of SDHB function was due to a reduction in mutant protein half-life, whereas colocalization of SDHB with mitochondria and immunoprecipitation with SDHA demonstrated intact subcellular localization and complex formation. The half-life of the SDHB protein increased after treatment with histone deacetylase inhibitors (HDACis), implicating the protein quality control machinery in the degradation of mutant SDHB protein. These findings provide the first direct mechanism of functional loss resulting from SDHB mutations and suggest that reducing protein degradation with HDACis may serve as a novel therapeutic paradigm for preventing the development of SDHB-related tumors.
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