title: Isoform-selective chemical inhibition of mDia-mediated actin assembly.
abstract: Formins are potent actin assembly factors. Diaphanous formins, including mDia1, mDia2, and mDia3 in mammals, are implicated in mitosis and cytokinesis, but no chemical interactors have been reported. We developed an in vitro screen for inhibitors of actin assembly by mDia1 and identified an inhibitor of mDia1 and mDia2 that does not inhibit mDia3 at the concentrations tested. These results establish the druggability of mDia formins and introduce a first-generation inhibitor.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Gauvin
authors.forename: Jami
authors.initials: J
authors.lastname: Fukui
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Peterson
authors.forename: Henry N
authors.initials: HN
authors.lastname: Higgs
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D005326:Fetal Proteins / Q000037:antagonists & inhibitors; D000080865:Formins; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D009252:NADPH Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011721:Pyrenes / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C108962:DIAPH1 protein, human; C491462:DIAPH2 protein, human; C491463:Diap2 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011721:Pyrenes; C508552:Dia2 protein, mouse; D009252:NADPH Dehydrogenase