ArticleThe Journal of biological chemistry2012
Hormone-induced 14-3-3γ adaptor protein regulates steroidogenic acute regulatory protein activity and steroid biosynthesis in MA-10 Leydig cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- The effects ofHeliyon · 2025Article
- Age-related testosterone decline: mechanisms and intervention strategies.Reproductive biology and endocrinology : RB&E · 2024Review
- Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1.Biomolecules · 2024Review
- Thromboxane AAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of STAR and SCP2/SCPx in the Transport of Cholesterol and Other Lipids.International journal of molecular sciences · 2022Review
- Differential mitochondrial protein interaction profile between human translocator protein and its A147T polymorphism variant.PloS one · 2022Article
- TSPO protein binding partners in bacteria, animals, and plants.Journal of bioenergetics and biomembranes · 2021Review
- High Throughput scRNA-Seq Provides Insights Into Leydig Cell Senescence Induced by Experimental Autoimmune Orchitis: A Prominent Role of Interstitial Fibrosis and Complement Activation.Frontiers in immunology · 2021Article
- Identification of Sec23ip, Part of 14-3-3γ Protein Network, as a Regulator of Acute Steroidogenesis in MA-10 Leydig Cells.Endocrinology · 2020Article
- STARD1 Functions in Mitochondrial Cholesterol Metabolism and Nascent HDL Formation. Gene Expression and Molecular mRNA Imaging Show Novel Splicing and a 1:1 Mitochondrial Association.Frontiers in endocrinology · 2020Review
- Leydig cells: formation, function, and regulation.Biology of reproduction · 2018Review
- VDAC1 at the crossroads of cell metabolism, apoptosis and cell stress.Cell stress · 2017Article
- Chimeric 14-3-3 proteins for unraveling interactions with intrinsically disordered partners.Scientific reports · 2017Article
- Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics.Frontiers in oncology · 2017Review
- Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies.Frontiers in endocrinology · 2016Review
- Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis.Molecular and cellular endocrinology · 2015Review
- Induction of androgen formation in the male by a TAT-VDAC1 fusion peptide blocking 14-3-3ɛ protein adaptor and mitochondrial VDAC1 interactions.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Protein modifications regulate the role of 14-3-3γ adaptor protein in cAMP-induced steroidogenesis in MA-10 Leydig cells.The Journal of biological chemistry · 2014Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Cholesterol is the sole precursor of steroid hormones in the body. The import of cholesterol to the inner mitochondrial membrane, the rate-limiting step in steroid biosynthesis, relies on the formation of a protein complex that assembles at the outer mitochondrial membrane called the transduceosome. The transduceosome contains several mitochondrial and cytosolic components, including the steroidogenic acute regulatory protein (STAR). Human chorionic gonadotropin (hCG) induces de novo synthesis of STAR, a process shown to parallel maximal steroid production. In the hCG-dependent steroidogenic MA-10 mouse Leydig cell line, the 14-3-3γ protein was identified in native mitochondrial complexes by mass spectrometry and immunoblotting, and its levels increased in response to hCG treatment. The 14-3-3 proteins bind and regulate the activity of many proteins, acting via target protein activation, modification and localization. In MA-10 cells, cAMP induces 14-3-3γ expression parallel to STAR expression. Silencing of 14-3-3γ expression potentiates hormone-induced steroidogenesis. Binding motifs of 14-3-3γ were identified in components of the transduceosome, including STAR. Immunoprecipitation studies demonstrate a hormone-dependent interaction between 14-3-3γ and STAR that coincides with reduced 14-3-3γ homodimerization. The binding site of 14-3-3γ on STAR was identified to be Ser-194 in the STAR-related sterol binding lipid transfer (START) domain, the site phosphorylated in response to hCG. Taken together, these results demonstrate that 14-3-3γ negatively regulates steroidogenesis by binding to Ser-194 of STAR, thus keeping STAR in an unfolded state, unable to induce maximal steroidogenesis. Over time 14-3-3γ homodimerizes and dissociates from STAR, allowing this protein to induce maximal mitochondrial steroid formation.
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Registered trials
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.