NDLI: Identification of a small molecule inhibitor of importin beta mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries

Content Provider	PubMed Central
Author	Martin, Hintersteiner Ambrus, Géza Bednenko, Janna Schmied, Mario Knox, Andrew J. S. Hubert, Gstach Seifert, Jan-marcus Singer, Eric L. Gerace, Larry Auer, Manfred
Abstract	In eukaryotic cells, proteins and RNA are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably leptomycin B. However, up to now no small molecule inhibitors of nuclear import have been described. Here we have used our automated Confocal Nanoscanning and bead picking method (CONA) for on-bead screening of a one bead/one compound library to identify the first such import inhibitor, karyostatin 1A. Karyostatin 1A binds importin β with high nanomolar affinity and specifically inhibits importin α/β mediated nuclear import at low micromolar concentrations in vitro and in living cells, without perturbing transportin mediated nuclear import or CRM1 mediated nuclear export. Surface plasmon resonance binding experiments suggest that karyostatin 1A acts by disrupting the interaction between importin β and the GTPase Ran. As a selective inhibitor of the importin α/β import pathway, karyostatin 1A will provide a valuable tool for future studies of nucleocytoplasmic trafficking.
Related Links	http://dx.doi.org/10.1021/cb100094k
Ending Page	979
Page Count	13
Starting Page	967
File Format	PDF
ISSN	15548929
e-ISSN	15548937
Journal	ACS chemical biology
Issue Number	10
Volume Number	5
Language	English
Publisher Date	2010-10-15
Access Restriction	Open
Subject Keyword	Molecular Medicine Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Molecular Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Importazole, a small molecule inhibitor of the transport receptor importin-β

Small molecule peptidomimetic inhibitors of importin α/β mediated nuclear transport

Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus

High-Throughput Screening of One-Bead-One-Compound Libraries: Identification of Cyclic Peptidyl Inhibitors against Calcineurin/NFAT Interaction

Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.

Nuclear import of Upf3p is mediated by importin-alpha/-beta and export to the cytoplasm is required for a functional nonsense-mediated mRNA decay pathway in yeast.

Antiviral Compounds Discovered by Virtual Screening of Small–Molecule Libraries against Dengue Virus E Protein

Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries

Identification and Characterization of a Small Molecule Inhibitor of Formin-Mediated Actin Assembly

Identification of a small molecule inhibitor of importin beta mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries

Similar Documents

Importazole, a small molecule inhibitor of the transport receptor importin-β

Small molecule peptidomimetic inhibitors of importin α/β mediated nuclear transport

Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus

High-Throughput Screening of One-Bead-One-Compound Libraries: Identification of Cyclic Peptidyl Inhibitors against Calcineurin/NFAT Interaction

Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus.

Nuclear import of Upf3p is mediated by importin-alpha/-beta and export to the cytoplasm is required for a functional nonsense-mediated mRNA decay pathway in yeast.

Antiviral Compounds Discovered by Virtual Screening of Small–Molecule Libraries against Dengue Virus E Protein

Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries

Identification and Characterization of a Small Molecule Inhibitor of Formin-Mediated Actin Assembly

Identification of a small molecule inhibitor of importin beta mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries