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Targeted kinase degradation via the KLHDC2 ubiquitin E3 ligase.
Kim Y, Seo P, Jeon E, You I, Hwang K, Kim N, Tse J, Bae J, Choi HS, Hinshaw SM, Gray NS, Sim T. Kim Y, et al. Cell Chem Biol. 2023 Nov 16;30(11):1414-1420.e5. doi: 10.1016/j.chembiol.2023.07.008. Epub 2023 Aug 10. Cell Chem Biol. 2023. PMID: 37567174
Peptide-based bivalent compounds that can induce proximity between KLHDC2 and target proteins cause degradation of the targeted factors. The cellular activity of these compounds depends on KLHDC2 binding. This work demonstrates the utility of KLHDC2 for targe …
Peptide-based bivalent compounds that can induce proximity between KLHDC2 and target proteins cause degradation of the targeted facto …
Identification of KLHDC2 as an efficient proximity-induced degrader of K-RAS, STK33, beta-catenin, and FoxP3.
Röth S, Kocaturk NM, Sathyamurthi PS, Carton B, Watt M, Macartney TJ, Chan KH, Isidro-Llobet A, Konopacka A, Queisser MA, Sapkota GP. Röth S, et al. Cell Chem Biol. 2023 Oct 19;30(10):1261-1276.e7. doi: 10.1016/j.chembiol.2023.07.006. Epub 2023 Aug 16. Cell Chem Biol. 2023. PMID: 37591251 Free article.
Here, using the affinity-directed protein missile (AdPROM) system, in which an anti-GFP nanobody was linked to an E3 ligase, we screened over 30 E3 ligases for their ability to degrade 4 target proteins, K-RAS, STK33, beta-catenin, and FoxP3, which were endogenously GFP-tagged. S …
Here, using the affinity-directed protein missile (AdPROM) system, in which an anti-GFP nanobody was linked to an E3 ligase, we screened ove …
E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity.
Scott DC, King MT, Baek K, Gee CT, Kalathur R, Li J, Purser N, Nourse A, Chai SC, Vaithiyalingam S, Chen T, Lee RE, Elledge SJ, Kleiger G, Schulman BA. Scott DC, et al. Mol Cell. 2023 Mar 2;83(5):770-786.e9. doi: 10.1016/j.molcel.2023.01.019. Epub 2023 Feb 16. Mol Cell. 2023. PMID: 36805027 Free PMC article.
True substrates capture the monomeric CRL2(KLHDC2), driving E3 activation by neddylation and subsequent substrate ubiquitylation. Non-substrates such as NEDD8 bind KLHDC2 with high affinity, but its slow on rate prevents productive association with CRL2(KLHDC2 …
True substrates capture the monomeric CRL2(KLHDC2), driving E3 activation by neddylation and subsequent substrate ubiquitylation. Non …
Co-opting the E3 ligase KLHDC2 for targeted protein degradation by small molecules.
Hickey CM, Digianantonio KM, Zimmermann K, Harbin A, Quinn C, Patel A, Gareiss P, Chapman A, Tiberi B, Dobrodziej J, Corradi J, Cacace AM, Langley DR, Békés M. Hickey CM, et al. Nat Struct Mol Biol. 2024 Feb;31(2):311-322. doi: 10.1038/s41594-023-01146-w. Epub 2024 Jan 4. Nat Struct Mol Biol. 2024. PMID: 38177675
To expand the roster of E3 ligases that can be utilized for TPD, we describe the discovery and biochemical characterization of small-molecule ligands targeting the E3 ligase KLHDC2. Furthermore, we functionalize these KLHDC2-targeting ligands into KLHDC2-base …
To expand the roster of E3 ligases that can be utilized for TPD, we describe the discovery and biochemical characterization of small-molecul …
A kelch motif-containing protein KLHDC2 regulates immune responses against Vibrio parahaemolyticus and white spot syndrome virus in Penaeus vannamei.
Yang L, Wang ZA, Geng R, Niu S, Zuo H, Weng S, He J, Xu X. Yang L, et al. Fish Shellfish Immunol. 2022 Aug;127:187-194. doi: 10.1016/j.fsi.2022.06.009. Epub 2022 Jun 16. Fish Shellfish Immunol. 2022. PMID: 35716970
The klhdc2 gene was widely expressed in shrimp tissues and its protein product was mainly present in the nucleus. ...Moreover, the regulatory effect of KLHDC2 on WSSV ie1 gene contributed to its negative effect on antiviral response. ...
The klhdc2 gene was widely expressed in shrimp tissues and its protein product was mainly present in the nucleus. ...Moreover, the re …
Recognition of the Diglycine C-End Degron by CRL2(KLHDC2) Ubiquitin Ligase.
Rusnac DV, Lin HC, Canzani D, Tien KX, Hinds TR, Tsue AF, Bush MF, Yen HS, Zheng N. Rusnac DV, et al. Mol Cell. 2018 Dec 6;72(5):813-822.e4. doi: 10.1016/j.molcel.2018.10.021. Mol Cell. 2018. PMID: 30526872 Free PMC article.
By hydrogen bonding with multiple backbone carbonyls of the peptides, KLHDC2 further locks in the otherwise degenerate degrons with a compact interface and unexpected high affinities. Our results reveal the structural mechanism by which KLHDC2 recognizes the simples …
By hydrogen bonding with multiple backbone carbonyls of the peptides, KLHDC2 further locks in the otherwise degenerate degrons with a …
Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2.
Chin KT, Xu HT, Ching YP, Jin DY. Chin KT, et al. Mol Cell Biochem. 2007 Feb;296(1-2):109-19. doi: 10.1007/s11010-006-9304-6. Epub 2006 Sep 9. Mol Cell Biochem. 2007. PMID: 16964437
In this study, we identified and characterized a paralog of KLHDC2 called KLHDC1. KLHDC1 and KLHDC2 share about 50% identity at the level of amino acid sequence and both gene loci localize to human chromosome 14q21.3. ...Thus, KLHDC1 and KLHDC2 have different …
In this study, we identified and characterized a paralog of KLHDC2 called KLHDC1. KLHDC1 and KLHDC2 share about 50% identity a …
Degronomics: Mapping the Interacting Peptidome of a Ubiquitin Ligase Using an Integrative Mass Spectrometry Strategy.
Canzani D, Rusnac DV, Zheng N, Bush MF. Canzani D, et al. Anal Chem. 2019 Oct 15;91(20):12775-12783. doi: 10.1021/acs.analchem.9b02331. Epub 2019 Sep 26. Anal Chem. 2019. PMID: 31525912 Free PMC article.
We report an integrative mass spectrometry (MS) strategy for characterizing protein fragments that interact with KLHDC2, a human E3 that recognizes the extreme C-terminus of substrates. ...These results significantly expand our understanding of the sequences that can be re …
We report an integrative mass spectrometry (MS) strategy for characterizing protein fragments that interact with KLHDC2, a human E3 t …
Differentially expressed genes in endothelial differentiation.
Ishii H, Mimori K, Mori M, Vecchione A. Ishii H, et al. DNA Cell Biol. 2005 Jul;24(7):432-7. doi: 10.1089/dna.2005.24.432. DNA Cell Biol. 2005. PMID: 16008511
By screening differentially expressed genes in mouse embryonic stem (ES) cells by subtractive hybridization, we identified three conserved but uncharacterized genes encoding bromodomain containing 3 (BRD3), protein lysine methyltransferase (PLM), and kelch domain containing 2 ( …
By screening differentially expressed genes in mouse embryonic stem (ES) cells by subtractive hybridization, we identified three conserved b …
14 results