Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1

E Noguchi; N Hayashi; Y Azuma; T Seki; M Nakamura; N Nakashima; M Yanagida; X He; U Mueller; S Sazer; T Nishimoto

Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1

EMBO J. 1996 Oct 15;15(20):5595-605.

Authors

E Noguchi¹, N Hayashi, Y Azuma, T Seki, M Nakamura, N Nakashima, M Yanagida, X He, U Mueller, S Sazer, T Nishimoto

Affiliation

¹ Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

PMID: 8896453
PMCID: PMC452304

Abstract

Using the two-hybrid method, we isolated a Saccharomyces cerevisiae cDNA encoding a protein homologous to Schizosaccharomyces pombe protein Dis3sp, using as bait, human GTPase Ran. The DIS3 gene is essential for viability and complements S.pombe mutant dis3-54 which is defective in mitosis. Although Dis3sc has no homology to RanBP1, it bound directly to Ran and the S.cerevisiae Ran homologue Cnr1, but not to the S.cerevisiae RCC1 homologue Srm1. Upon binding to Ran with a 1:1 molar ratio, Dis3sc enhanced a nucleotide-releasing activity of RCC1 on Ran. In the presence of Dis3sc, the K(m) of RCC1 on Ran decreased by half, while the kcat was unchanged. In vivo, Dis3sp was present as oligomers of M(r) 670-200 kDa as previously reported, and the 200 kDa oligomer of Dis3sp was found to include Spi1 and Pim1, the S.pombe homologues of Ran and RCC1, respectively. Although the biological function of the heterotrimeric oligomer consisting of Dis3, Spi1 and Pim1 is unknown, our results indicate that Dis3 is a component of the RCC1-Ran pathway.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Bacterial Proteins / metabolism*
Bacterial Toxins*
Cell Cycle Proteins*
DNA, Complementary / chemistry
DNA-Binding Proteins / metabolism*
Escherichia coli Proteins*
Exoribonucleases
Exosome Multienzyme Ribonuclease Complex
Fungal Proteins / metabolism*
GTP-Binding Proteins / metabolism*
Guanine Nucleotide Exchange Factors*
Humans
Kinetics
Membrane Proteins*
Mitosis*
Molecular Sequence Data
Molecular Weight
Monomeric GTP-Binding Proteins*
Nuclear Proteins / metabolism*
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins*
Schizosaccharomyces
Schizosaccharomyces pombe Proteins
Sequence Alignment
Sequence Homology, Amino Acid
ran GTP-Binding Protein

Substances

Bacterial Proteins
Bacterial Toxins
Cell Cycle Proteins
DNA, Complementary
DNA-Binding Proteins
Escherichia coli Proteins
Fungal Proteins
GSP1 protein, S cerevisiae
Guanine Nucleotide Exchange Factors
Membrane Proteins
Nuclear Proteins
RCC1 protein, human
SRM1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Schizosaccharomyces pombe Proteins
HokC protein, E coli
Exoribonucleases
Exosome Multienzyme Ribonuclease Complex
DIS3 protein, S cerevisiae
dis3 protein, S pombe
GTP-Binding Proteins
Monomeric GTP-Binding Proteins
ran GTP-Binding Protein

Associated data

GENBANK/D76430