Ask about this productRelated genes to: CUL1 Blocking Peptide
- Gene:
- CUL1 NIH gene
- Name:
- cullin 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-10-29
- Date modifiied:
- 2014-11-19
Related products to: CUL1 Blocking Peptide
Related articles to: CUL1 Blocking Peptide
- Ethylene signaling is essential for apical hook formation during early seedling development in darkness, protecting cotyledons and shoot apical meristem as seedlings emerge through soil. ETHYLENE-INSENSITIVE 3 (EIN3), a central transcription factor in this pathway, activates ethylene-responsive genes such as HOOKLESS1 (HLS1) to promote hook formation. EIN3 is rapidly stabilized in response to ethylene but is otherwise targeted for degradation by the F-box proteins EIN3-BINDING F BOX PROTEIN 1 (EBF1) and EBF2. Here, we demonstrate that HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 15 (HOS15), a substrate receptor for both SCF/CUL1 and CUL4-DDB1 E3 ubiquitin ligase complexes, functions as a negative regulator of EIN3 protein stability. Loss-of-function mutation of HOS15 (hos15-2) resulted in enhanced apical hook curvature upon treatment with the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). In these mutants, ethylene-induced HLS1 transcript levels were significantly higher than those in wild-type plants, indicating that HOS15 suppresses ethylene-mediated hook formation. HOS15 interacts with EIN3 in planta and promotes its destabilization. Furthermore, the hos15-2 ein3-1 double mutant exhibited reduced hook curvature and lower expression of HLS1 and ETHYLENE RESPONSIVE FACTOR 1 (ERF1) compared with hos15-2 alone, indicating that EIN3 functions downstream of HOS15. These findings establish HOS15 as a key modulator of ethylene signaling, fine-tuning EIN3 protein stability during apical hook development in Arabidopsis thaliana. - Source: PubMed
Publication date: 2026/04/24
Khan Haris AliAhn GyeongikAulia Ade CitraSari Septi AnitaShin Gyeong-ImJeong Song YiHuh Jin-SungJi Myung GeunChoi BongsooKim YoungjuPark JunghoonYoon Gyeong MeeKim Min GabKim Woe-YeonYun Dae-JinCha Joon-Yung - Targeted protein degradation (TPD) through the ubiquitin-proteasome system is driven by compound-mediated polyubiquitination of a protein-of-interest by an E3 ubiquitin (Ub) ligase. Relatively few E3s have been successfully utilized for TPD and the governing principles of functional ternary complex formation between the E3, degrader, and protein target remain elusive. FBXO22 has recently been harnessed for TPD applications by degraders that covalently modify its cysteine residues. Here, we reveal that the aldehyde derivative of UNC10088 promotes cooperative binding of FBXO22 to NSD2, a histone methyltransferase and oncogenic protein, leading to a cryo-EM structure of the SKP1-CUL1-F-box (SCF)-FBXO22 complex with NSD2. This structure revealed a conformational change in the FBXO22 loop surrounding C326, further exposing the cysteine for covalent recruitment. Additional medicinal chemistry efforts led to the discovery of benzaldehyde-based non-prodrug degraders that similarly engage C326 of FBXO22 and potently degrade NSD2. Unlike many degraders, our molecules recruit NSD2 to a different surface of FBXO22 than the known FBXO22 substrate BACH1, allowing for concurrent complex formation and structural determination of SCF bound to both the neosubstrate NSD2 and native substrate BACH1. Overall, we demonstrate the biochemical and structural basis for NSD2 degradation, revealing key principles for efficient and selective TPD by SCF. - Source: PubMed
Publication date: 2026/04/23
Robertson Kevin CAmann Sascha JLiu TongkunFunk Adam VWang XianxiGrishkovskaya IrinaMehmood AamirTabor John RNorris-Drouin Jacqueline LArrowsmith Cheryl HCollins Jon LMiao YinglongEmanuele Michael JHaselbach DavidJames Lindsey IBrown Nicholas G - Carnosine, an imidazole dipeptide, has potential for treating neurodegenerative diseases, including Parkinson's disease. However, carnosine-degrading enzymes limit its bioavailability. In this study, we established a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced Parkinson's disease and intranasally administered balenine, a carnosine analog featuring a methylated imidazole that is resistant to degradation enzymes, to target the brain via the olfactory epithelium. MPTP + balenine-treated mice demonstrated improved recognition scores in the object location test. They also exhibited a significantly increased tyrosine hydroxylase-positive cells and reduced expression of glial fibrillary acidic protein, an inflammatory marker, indicating that balenine mitigated neurodegenerative damage and inflammation in mice with MPTP-induced Parkinson's disease. Proteomic analysis revealed that activation of the KEAP1-NFE2L2 pathway, neddylation, and GSK3B and BTRC:CUL1-mediated degradation of NFE2L2. Collectively, these results highlight the efficacy of intranasal drops of balenine in Parkinson's disease and their potential to improve neurodegenerative disease prognosis. - Source: PubMed
Publication date: 2026/04/16
Chukai YusakuArisumi KonatsuYasunaga GentaSakai HirokiTatara YotaKasai ShuyaYamashita TetsuroIshiyama EriKiyokawa KokoroOzaki Taku - Protein phosphatase 2A (PP2A) is a Ser/Thr phosphatase that regulates the phosphorylation of almost all cellular processes, including cell division and proliferation. PP2A forms heterotrimeric holoenzyme complexes comprising a catalytic subunit (PP2Ac), a scaffolding subunit (PP2Aa) and variable B regulatory subunits that exert precise control over enzyme substrate specificity and prevent indiscriminate dephosphorylation of phosphoproteins. However, the mechanisms that control the activity of uncomplexed catalytic subunits have remained relatively unclear. Here we find that the E3 ligase SKP1-CUL1-F-box (SCF) complex containing F-box other protein 42 (FBXO42, also known as JFK; hereafter, SCF) degrades holoenzyme-free PP2Ac in a complex with the coiled-coil protein CCDC6 to maintain cancer cell fitness. The cryo-electron microscopy structure of the FBXO42-CCDC6-PP2Ac assembly reveals a pseudosymmetric architecture in which CCDC6 forms a central dimeric template that recruits multiple copies of PP2Ac and creates a substrate for FBXO42. Both the quaternary structure of this CCDC6-PP2Ac heterodimer and the post-translationally methylated tail of PP2Ac are recognized by FBXO42 for ubiquitination. The multivalent structure facilitated by CCDC6 enables the assembly of multiple degradation complexes along a single coiled coil, leading to the turnover of free phosphatases and downregulation of catalytic activity. Together, our findings define a mechanism for PP2A control through the ubiquitin-proteosome system and establish a paradigm for cullin-RING ligase-substrate interactions. - Source: PubMed
Publication date: 2026/04/15
Coassolo SebastienMichaelian NairieMaculins TimursAzumaya Caleigh MCheung Tommy KYin JianpingZilberleyb InnaPahuja Kanika BajajGarner ThomasLau TedMau DavisGrimmer MatthewFortin Jean-PhilippeCosta MikeDimitrova Yoana NRose Christopher MHsu Peter LYauch Robert L - Six new copper(ii) complexes with general molecular formula [CuL1(Phen)] (1), [CuL2(Phen)] (2), [CuL3(Phen)] (3), [CuL1(DM-Phen)] (4), [CuL2(DM-Phen)] (5) and [CuL3(DM-Phen)] (6) (L = ()-1-(((4-chloro-2-hydroxyphenyl)imino)methyl)naphthalen-2-ol (L1), ()-1-(((2-hydroxy-5-methylphenyl)imino)methyl)naphthalen-2-ol (L2), ()-1-(((2-hydroxy-4-nitrophenyl)imino)methyl)naphthalen-2-ol (L3), Phen = 1,10-phenanthroline and DM-Phen = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized by spectroscopic as well as crystallographic techniques. Molecular structures of 2, 4, 5 and 6 revealed that they are mononuclear species where the copper(ii) center is five-coordinated to a pair of oxygen atoms as well as one nitrogen atom from the ligands (L1-L3) and to a pair of nitrogen atoms from the auxiliary ligand (Phen or DM-Phen) conforming to a distorted square pyramid. The binding affinities of ligands L1-L3 and copper(ii) complexes 1-6 with calf thymus DNA (ctDNA) and bovine serum albumin (BSA) were evaluated using UV-visible absorption spectroscopy. For ctDNA, all compounds showed hypochromism and bathochromic shifts suggesting intercalative binding, with values ranging from 1.49 × 10 to 2.74 × 10 M. The complexes exhibited 3-18-fold higher affinity than ligands, especially those with 2,9-dimethyl-1,10-phenanthroline coligands. BSA titrations of complexes 1-6 revealed hyperchromic shifts at ∼280 nm, with values of 9.59 × 10 to 2.41 × 10 M. These moderate-to-strong bindings were enhanced by lipophilic substituents that promote hydrophobic and π-stacking interactions in protein pockets. All of the compounds inhibit α-amylase better than acarbose with complex 5 (IC = 0.274 mM) showing the highest activity. For the α-glucosidase assay, only complexes 2 (IC = 0.055 mM) and 4 (IC = 0.054 mM) outshined acarbose (IC = 0.059 mM) while other compounds showed moderate to good α-glucosidase inhibition activity. Antioxidant activities of the free ligands showed better activity than that of the metal complexes with none of the compounds performing better than quercetin in all of the assays explored for this study. - Source: PubMed
Publication date: 2026/04/10
Oladipo Segun DAdeleke Adesola AOlofisan Kolawole AOmondi BernardLuckay Robert C