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PMID: 19764708 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Isoform-selective chemical inhibition of mDia-mediated actin assembly.

Biochemistry ·Vol. 48 ·No. 40 ·2009-10-13 ·Pages 9327-9

Gauvin TJ, Fukui J, Peterson JR, Higgs HN

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.

MeSH Terms
Actins/antagonists & inhibitors,metabolism Adaptor Proteins, Signal Transducing/antagonists & inhibitors,chemistry,physiology Animals Carrier Proteins/antagonists & inhibitors,chemistry,physiology Fetal Proteins/antagonists & inhibitors Formins Humans Mice Microfilament Proteins/antagonists & inhibitors Microtubule-Associated Proteins/antagonists & inhibitors,chemistry,physiology NADPH Dehydrogenase/antagonists & inhibitors,chemistry,physiology Nuclear Proteins/antagonists & inhibitors Protein Isoforms/antagonists & inhibitors,chemistry,physiology Protein Structure, Tertiary/physiology Pyrenes/chemistry Sequence Homology, Amino Acid
Chemicals
Actins Adaptor Proteins, Signal Transducing Carrier Proteins DIAPH1 protein, human DIAPH2 protein, human Diap2 protein, mouse Fetal Proteins Formins Microfilament Proteins Microtubule-Associated Proteins Nuclear Proteins Protein Isoforms Pyrenes Dia2 protein, mouse NADPH Dehydrogenase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gauvin Timothy J
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Fukui Jami
Peterson Jeffrey R
Higgs Henry N
References (11)
11 references, click to expand
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Article Info
Journal
Biochemistry
Abbr.
Biochemistry
ISSN
1520-4995
DOI
10.1021/bi901354z
Published
2009-10-13
Pages
9327-9
Language
English
Region
United States
NLM ID
0370623
PMCID
PMC2758331
Subset
IM
Grants
NIGMS NIH HHS · GM083025 · United States
NIGMS NIH HHS · R01 GM083025 · United States
NINDS NIH HHS · R21 NS059359 · United States
NIGMS NIH HHS · R01 GM069818 · United States
NIGMS NIH HHS · R01 GM069818-05 · United States
NIGMS NIH HHS · GM069818 · United States
NINDS NIH HHS · NS059359 · United States
External Links
PubMed source DOI: 10.1021/bi901354z PMC Full Text View journal details
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