ArticleThe Journal of biological chemistry2012
Selective proteasomal degradation of the B'β subunit of protein phosphatase 2A by the E3 ubiquitin ligase adaptor Kelch-like 15.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Defining E3 ligase-substrate relationships through multiplex CRISPR screening.Nature cell biology · 2023Article
- Elucidation of E3 ubiquitin ligase specificity through proteome-wide internal degron mapping.Molecular cell · 2023Article
- X-linked intellectual disability related to a novel variant of KLHL15.Human genome variation · 2023Article
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Kelch-like proteins in the gastrointestinal tumors.Acta pharmacologica Sinica · 2023Review
- Endothelial Cullin3 Mutation Impairs Nitric Oxide-Mediated Vasodilation and Promotes Salt-Induced Hypertension.Function (Oxford, England) · 2022Article
- The roles of KLHL family members in human cancers.American journal of cancer research · 2022Review
- Cullin-3: Renal and Vascular Mechanisms Regulating Blood Pressure.Current hypertension reports · 2020Review
- A robust and economical pulse-chase protocol to measure the turnover of HaloTag fusion proteins.The Journal of biological chemistry · 2019Article
- LITAF (Lipopolysaccharide-Induced Tumor Necrosis Factor) Regulates Cardiac L-Type Calcium Channels by Modulating NEDD (Neural Precursor Cell Expressed Developmentally Downregulated Protein) 4-1 Ubiquitin Ligase.Circulation. Genomic and precision medicine · 2019Article
- Differential Expression of Genes for Ubiquitin Ligases in Medulloblastoma Subtypes.Cerebellum (London, England) · 2019Article
- Control of mTOR signaling by ubiquitin.Oncogene · 2019Review
- Protein phosphatase 2A Aα regulates Aβ protein expression and stability.The Journal of biological chemistry · 2019Article
- Functional analysis of Cullin 3 E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- Atypical Protein Phosphatase 2A Gene Families Do Not Expand via Paleopolyploidization.Plant physiology · 2017Article
- Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection.Nature communications · 2016Article
- Quantitative proteomics reveals novel protein interaction partners of PP2A catalytic subunit in pancreatic β-cells.Molecular and cellular endocrinology · 2016Article
- X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.Molecular psychiatry · 2016Article
- Array-based molecular karyotyping in fetuses with isolated brain malformations identifies disease-causing CNVs.Journal of neurodevelopmental disorders · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein phosphatase 2A (PP2A), a ubiquitous and pleiotropic regulator of intracellular signaling, is composed of a core dimer (AC) bound to a variable (B) regulatory subunit. PP2A is an enzyme family of dozens of heterotrimers with different subcellular locations and cellular substrates dictated by the B subunit. B'β is a brain-specific PP2A regulatory subunit that mediates dephosphorylation of Ca(2+)/calmodulin-dependent protein kinase II and tyrosine hydroxylase. Unbiased proteomic screens for B'β interactors identified Cullin3 (Cul3), a scaffolding component of E3 ubiquitin ligase complexes, and the previously uncharacterized Kelch-like 15 (KLHL15). KLHL15 is one of ∼40 Kelch-like proteins, many of which have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases. Here, we report that KLHL15-Cul3 specifically targets B'β to promote turnover of the PP2A subunit by ubiquitylation and proteasomal degradation. Comparison of KLHL15 and B'β tissue expression profiles suggests that the E3 ligase adaptor contributes to selective expression of the PP2A/B'β holoenzyme in the brain. We mapped KLHL15 residues critical for homodimerization as well as interaction with Cul3 and B'β. Explaining PP2A subunit selectivity, the divergent N terminus of B'β was found necessary and sufficient for KLHL15-mediated degradation, with Tyr-52 having an obligatory role. Although KLHL15 can interact with the PP2A/B'β heterotrimer, it only degrades B'β, thus promoting exchange with other regulatory subunits. E3 ligase adaptor-mediated control of PP2A holoenzyme composition thereby adds another layer of regulation to cellular dephosphorylation events.
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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.