Identification of seco‐clavilactone B as a small‐molecule actin polymerization inhibitor

Miyazaki, So; Sasazawa, Yukiko; Mogi, Takuma; Suzuki, Takehiro; Yoshida, Keisuke; Dohmae, Naoshi; Takao, Ken Ichi; Simizu, Siro

doi:10.1002/1873-3468.12154

Cited by 19 publications

(12 citation statements)

References 41 publications

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“…Signals were detected with ECL using Western Lightning Plus-ECL (PerkinElmer, Inc., Waltham, MA, USA) and Immobilon Western Chemiluminescent HRP substrates (Merck KGaA). Protein bands were quantified in ImageJ (National Institutes of Health, Bethesda, MD, USA) [ 34 , 35 , 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

et al. 2021

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DPY19L3 has been identified as a C-mannosyltransferase for thrombospondin type-1 repeat domain-containing proteins. In this study, we focused on the role of DPY19L3 in the myogenic differentiation of C2C12 mouse myoblast cells. We carried out DPY19L3 gene depletion using the CRISPR/Cas9 system. The result showed that these DPY19L3-knockout cells could not be induced for differentiation. Moreover, the phosphorylation levels of MEK/ERK and p70S6K were suppressed in the DPY19L3-knockout cells compared with that of parent cells, suggesting that the protein(s) that is(are) DPY19L3-mediated C-mannosylated and regulate(s) MEK/ERK or p70S6K signaling is(are) required for the differentiation.

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Section: Methodsmentioning

confidence: 99%

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

et al. 2021

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“…Cell culture. HT1080 human fibrosarcoma (Japanese Collection of Research Bioresources Cell Bank, Osaka, Japan), 293T (RIKEN BioResource Center, Tsukuba, Japan), A549 human lung adenocarcinoma (RIKEN BioResource Center) (37)(38)(39)(40), PANC1 human pancreatic adenocarcinoma (RIKEN BioResource Center) and MDA-MB-231 human breast adenocarcinoma cell lines, which was gifted by Professor Masakazu Toi (Kyoto University Graduate School of Medicine, Kyoto, Japan), were all cultured in Dulbecco's modified Eagle's medium (DMEM; Nissui Pharmaceutical Co., Ltd, Tokyo, Japan) supplemented with 6% (v/v) fetal bovine serum (Cosmo Bio Co. Ltd., Tokyo, Japan), 100 U/ml penicillin G, 100 mg/l kanamycin, 600 mg/l L-glutamine, and 2.25 g/l NaHCO 3 at 37˚C in a humidified incubator with 5% CO 2 . The LoVo human colon adenocarcinoma cell line was cultured in RPMI-1640 medium (Nissui Pharmaceutical Co., Ltd) supplemented with 10% (v/v) fetal bovine serum, 105 U/ml penicillin G, 105 mg/l kanamycin, 314 mg/l L-glutamine, and 2.25 g/l NaHCO 3 at 37˚C in a humidified incubator with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

C‑mannosylation of R‑spondin2 activates Wnt/β‑catenin signaling and migration activity in human tumor cells

et al. 2019

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, one of the four members of the R-spondin family of proteins, has agonistic activity in the Wnt/β-catenin signaling pathway, and it is associated with normal development, as well as disease, such as cancer. The present study focused on the C-mannosylation of Rspo2, which is a novel and unique type of glycosylation that occurs via a C-C linkage between the tryptophan residue and an α-mannose. Although Rspo2 has two putative C-mannosylation sites at residues Trp 150 and Trp 153 , it had not been reported to date whether these sites are C-mannosylated. Firstly, results from mass spectrometry demonstrated that Rspo2 was C-mannosylated at the Trp 150 and Trp 153 residues. Notably, while this C-mannosylation of Rspo2 resulted in increased extracellular secretion in human fibrosarcoma HT1080 cells, in other human tumor cell lines it inhibited secretion. However, C-mannosylation had consistent effects on the activation of Wnt/β-catenin signaling in PANC1 and MDA-MB-231 cells, as well as HT1080 cells. Furthermore, overexpression of wild-type Rspo2 significantly increased the migratory ability of A549 and HT1080 cells, whereas overexpression of a C-mannosylation-defective mutant enhanced migration to a lesser degree. These results suggested that C-mannosylation of Rspo2 may promote cancer progression and that the inhibition of C-mannosylation may serve as a potential novel therapeutic approach for cancer therapy.

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“…Next, we completed the enantioselective total synthesis of the natural enantiomers of 1 and 2 . In collaborative research with a biology group, we showed that synthetic analog 6 , called seco‐clavilactone B, is a novel actin polymerization inhibitor and can serve as a bioprobe for clarifying cytoskeletal dynamics . Later, two total syntheses of clavilactones were published by the Li group and the Yoshimitsu group .…”

Section: Figurementioning

confidence: 99%

Total Synthesis and Structural Revision of Clavilactone D

Takao

Nemoto

Mori

et al. 2017

Chemistry A European J

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A structural revision of clavilactone D, a potent inhibitor of protein tyrosine kinases, was achieved by total syntheses of two newly proposed structures. The syntheses relied on ring-opening/ring-closing metathesis, which transformed a cyclobutenecarboxylate into a γ-butenolide. The syntheses confirmed that the correct structure of clavilactone D has an amino group at C-3 instead of a hydroxy group at C-2 in the originally proposed structure.

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Identification of seco‐clavilactone B as a small‐molecule actin polymerization inhibitor

Cited by 19 publications

References 41 publications

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts

C‑mannosylation of R‑spondin2 activates Wnt/β‑catenin signaling and migration activity in human tumor cells

Total Synthesis and Structural Revision of Clavilactone D

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