ArticleBMC neuroscience2011
Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation.
Article in BMC neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Effect of photoperiod on the feline adipose transcriptome as assessed by RNA sequencing.BMC veterinary research · 2014Trial
- The Roles of Obesity and ASB4 in Preeclampsia Pathogenesis.International journal of molecular sciences · 2024Review
- Insulin Elevates ID2 Expression in Trophoblasts and Aggravates Preeclampsia in Obese ASB4-Null Mice.International journal of molecular sciences · 2023Article
- Observational
- An examination of multiple classes of rare variants in extended families with bipolar disorder.Translational psychiatry · 2018Article
- The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells.Chinese journal of cancer · 2017Article
- The role of cullin 5-containing ubiquitin ligases.Cell division · 2016Review
- The ubiquitin ligase ASB4 promotes trophoblast differentiation through the degradation of ID2.PloS one · 2014Article
- Clustering of transcriptional profiles identifies changes to insulin signaling as an early event in a mouse model of Alzheimer's disease.BMC genomics · 2013Article
- Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases.Journal of molecular biology · 2013Article
- Article
- Brain-specific homeobox factor as a target selector for glucocorticoid receptor in energy balance.Molecular and cellular biology · 2013Article
- A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling.Journal of neuroendocrinology · 2013Article
- Ankyrin repeat and suppressor of cytokine signaling box containing protein-10 is associated with ubiquitin-mediated degradation pathways in trabecular meshwork cells.Molecular vision · 2013Article
- Effect of IRS4 levels on PI 3-kinase signalling.PloS one · 2013Article
- The Role of Elongin BC-Containing Ubiquitin Ligases.Frontiers in oncology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4) is expressed in neuropeptide Y and proopiomelanocortin (POMC) neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s) of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4) is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling.
resultsIn situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308.
conclusionsThese data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.
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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.