Abstract:
:In addition to previously isolated ratjadone A we describe three new members of this family, ratjadones B, C, and D, from another strain of the myxobacterium Sorangium cellulosum. We have investigated the properties of these ratjadones with respect to their activity on mammalian cell lines. We found IC(50) values in the picomolar range and a significant increase in the size of nuclei. A further examination showed that they inhibit the export of the leucine-rich nuclear export signal (LR-NES) containing proteins in different cell lines. Ratjadones are able to inhibit the formation of the nuclear export complex composed of the CRM1, RanGTP, and the cargo protein, as shown by two different in vitro assays. Finally, the binding of ratjadone C to CRM1 was demonstrated. These ratjadone activities are in the same concentration range as described for the polyketide leptomycin B (LMB) from Streptomyces sp. Like LMB, it seems that the ratjadones covalently bind to CRM1, inhibit cargo protein binding via LR-NES, and thereby block nuclear export. Thus, the ratjadones represent a new class of natural compounds which inhibit proliferation in eukaryotes by blocking nuclear export.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Köster M,Lykke-Andersen S,Elnakady YA,Gerth K,Washausen P,Höfle G,Sasse F,Kjems J,Hauser Hdoi
10.1016/s0014-4827(03)00100-9keywords:
subject
Has Abstractpub_date
2003-06-10 00:00:00pages
321-31issue
2eissn
0014-4827issn
1090-2422pii
S0014482703001009journal_volume
286pub_type
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