+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RRM proteins interacting with the cap region of topoisomerase I

RRM proteins interacting with the cap region of topoisomerase I

Journal of Molecular Biology 369(4): 1098-1112

RNA recognition motif (RRM) domains bind both nucleic acids and proteins. Several proteins that contain two closely spaced RRM domains were previously found in protein complexes formed by the cap region of human topoisomerase 1, a nuclear enzyme responsible for DNA relaxation or phosphorylation of SR splicing proteins. To obtain molecular insight into specific interactions between the RRM proteins and the cap region of topo I we examined their binary interactions using the yeast two-hybrid system. The interactions were established for hnRNP Al, p54(nrb), and SF2/ASF, but not for hnRNP L or HuR. To identify the amino acid pattern responsible for binding, experimental mutagenesis was employed and computational modelling of these processes was carried out. These studies revealed that two RRM domains and six residues of the consensus sequence are required for the binding to the cap region. On the basis of the above data, a structural model for the hnRNP Al-topoisomerase I complex was proposed. The main component of the hnRNP Al binding site is a hydrophobic pocket on the beta-surface of the first RRM domain, similar to that described for Y14 protein interacting with Mago. We demonstrated that the interaction between RRM domains and the cap region was important for the kinase reaction catalyzed by topoisomerase 1. Together with the previously described inhibitory effect of RRM domains of SF2 / ASF on DNA cleavage, the above suggests that the binding of RRM proteins could regulate the activity of topoisomerase 1.

(PDF emailed within 0-6 h: $19.90)

Accession: 055338659

Download citation: RISBibTeXText

PMID: 17481653

DOI: 10.1016/j.jmb.2007.04.017

Related references

Identification and characterization of the genes for two topoisomerase I-interacting proteins from Saccharomyces cerevisiae. Yeast 15(1): 35-41, 1999

Differential inhibition of the catalytic and cleavage activities of topoisomerase by a series of established and novel topoisomerase-interacting agents. Proceedings of the American Association for Cancer Research Annual Meeting 36(0): 443, 1995

Differential sensitivities of recombinant human topoisomerase IIalpha and beta to various classes of topoisomerase II-interacting agents. Biochemical Pharmacology 56(4): 503-507, 1998

Differential in vitro interactions of a series of clinically useful topoisomerase-interacting compounds with the cleavage/religation activity of the human topoisomerase IIalpha and IIbeta isoforms. Anti-Cancer Drugs 10(6): 551-560, 2000

Brain proteins interacting with the tetramerization region of non-erythroid alpha spectrin. Cellular & Molecular Biology Letters 12(4): 604-620, 2007

Analyses of the functional region of 6b protein on T-DNA of A tumefaciens and the role of its interacting proteins. Plant & Cell Physiology 42(Supplement): s66, 2001

Interacting proteins for the bZIP transcriptional factor, RSG that binds to auxin-responsive region. Plant & Cell Physiology 39(SUPPL ): S58, 1998

Detection of cellular proteins and viral core protein interacting with the 5' untranslated region of hepatitis C virus RNA. Journal of Biomedical Science 2(3): 227-236, 1995

ATG8 family proteins act as scaffolds for assembly of the ULK complex: sequence requirements for LC3-interacting region (LIR) motifs. Journal of Biological Chemistry 287(47): 39275-39290, 2013

A novel point mutation in the 3' flanking region of the DNA-binding domain of topoisomerase II alpha associated with acquired resistance to topoisomerase II active agents. Oncology Research 7(1): 21-29, 1995

Phenobarbitone-mediated translocation of the cytosolic proteins interacting with the 5'-proximal region of rat liver CYP2B1/B2 gene into the nucleus. Biochemical and Biophysical Research Communications 292(2): 312-317, 2002

Nuclear proteins interacting with the promoter region of the human granulocyte/macrophage colony-stimulating factor gene. Proceedings of the National Academy of Sciences of the United States of America 85(3): 674-678, 1988

Molecular epidemiological study on pre-X region of hepatitis B virus and identification of hepatocyte proteins interacting with whole-X protein by yeast two-hybrid. World Journal of Gastroenterology 11(22): 3473-3478, 2005