ArticleThe Journal of biological chemistry2012
Endopeptidase cleavage generates a functionally distinct isoform of C1q/tumor necrosis factor-related protein-12 (CTRP12) with an altered oligomeric state and signaling specificity.
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 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Impact of spinach thylakoid extract-induced 12-week high-intensity functional training on specific adipokines in obese males.Journal of the International Society of Sports Nutrition · 2024Trial
- CTRP12 in cardiovascular and metabolic diseases: current status and future perspective.Frontiers in cardiovascular medicine · 2026Review
- Understanding the Role of Adipokines in Cardiometabolic Dysfunction: A Review of Current Knowledge.Biomolecules · 2025Review
- N-terminal domain of CTRP9 promotes cardiac fibroblast activation in myocardial infarction via Rap1/Mek/Erk pathway.Journal of translational medicine · 2025Article
- Impact of using supplemented thylakoids derived from spinach for 12 weeks of high-intensity functional training on adipo-myokines in obese males.Frontiers in nutrition · 2025Article
- CTRP12 ameliorates post-myocardial infarction heart failure through down-regulation of cardiac apoptosis, oxidative stress and inflammation by influencing the TAK1-p38 MAPK/JNK pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Prospects of potential adipokines as therapeutic agents in obesity-linked atherogenic dyslipidemia and insulin resistance.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2023Review
- Complement 1q/Tumor Necrosis Factor-Related Proteins (CTRPs): Structure, Receptors and Signaling.Biomedicines · 2023Review
- A study on serum pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG) levels in patients with acromegaly.Journal of endocrinological investigation · 2022Article
- Protein Modifications Critical for Myonectin/Erythroferrone Secretion and Oligomer Assembly.Biochemistry · 2020Article
- Adipolin/C1q/Tnf-related protein 12 prevents adverse cardiac remodeling after myocardial infarction.PloS one · 2020Article
- N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.Biochemistry · 2019Article
- Indel detection from Whole Genome Sequencing data and association with lipid metabolism in pigs.PloS one · 2019Article
- Structural commonality of C1q TNF-related proteins and their potential to activate relaxin/insulin-like family peptide receptor 1 signalling pathways in cancer cells.British journal of pharmacology · 2017Review
- CTRP7 deletion attenuates obesity-linked glucose intolerance, adipose tissue inflammation, and hepatic stress.American journal of physiology. Endocrinology and metabolism · 2017Article
- Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity.Scientific reports · 2017Article
- Partial deficiency of CTRP12 alters hepatic lipid metabolism.Physiological genomics · 2016Article
- Adipocytokines in Cardiovascular and Metabolic Diseases.Journal of atherosclerosis and thrombosis · 2016Review
- CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- C1q-TNF-related protein-9, a novel cardioprotetcive cardiokine, requires proteolytic cleavage to generate a biologically active globular domain isoform.American journal of physiology. Endocrinology and metabolism · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Adipose tissue-derived adipokines are an important class of secreted metabolic regulators that mediate tissue cross-talk to control systemic energy balance. We recently described C1q/TNF-related protein-12 (CTRP12), a novel insulin-sensitizing adipokine that regulates glucose metabolism in liver and adipose tissue. However, the biochemical properties of CTRP12 and its naturally occurring cleaved isoform have not been characterized. Here, we show that CTRP12 is a secreted hormone subjected to multiple functionally relevant posttranslational modifications at highly conserved residues. For example, Asn(39) is glycosylated, whereas Cys(85) mediates the assembly of higher order oligomeric structure. Endopeptidase cleavage at Lys(91) generates a cleaved globular gCTRP12 isoform, the expression of which is increased by insulin. PCSK3/furin was identified as the major proprotein convertase expressed by adipocytes that mediates the endogenous cleavage of CTRP12. Cleavage at Lys(91) is context-dependent: mutation of the charged Arg(93) to Ala on the P2' position enhanced cleavage, and triple mutations (K90A/K91A/R93A) abolished cleavage. Importantly, the two isoforms of CTRP12 differ in oligomeric structures and are functionally distinct. The full-length protein forms trimers and larger complexes, and the cleaved isoform consisted of predominantly dimers. Whereas full-length fCTRP12 strongly activated Akt signaling in H4IIE hepatocytes and 3T3-L1 adipocytes, gCTRP12 preferentially activated MAP kinase (ERK1/2 and p38 MAPK) signaling. Further, only fCTRP12 improved insulin-stimulated glucose uptake in adipocytes. These results reveal a novel mechanism controlling signaling specificity and function of a hormone via cleavage-dependent alteration in oligomeric state.
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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.