Disease relevance of Fs(2)Ket

• The Ketel(+) transgenes rescue ketel(r)-associated zygotic lethality and slightly reduce Ketel(D)-associated dominant female sterility [1].

High impact information on Fs(2)Ket

• Here, we report the three-dimensional structure of a complex between Ran bound to the nonhydrolyzable GTP analog GppNHp and a 462-residue fragment from Importin beta [2].
• The structure of Importin beta shows 10 tandem repeats resembling HEAT and Armadillo motifs [2].
• Transport receptors of the Importin beta family shuttle between the nucleus and cytoplasm and mediate transport of macromolecules through nuclear pore complexes [2].
• Importin alpha binds to classical nuclear localization signal (cNLS)-containing proteins and links them to importin beta, the karyopherin that ferries the ternary complex through the NPC [3].
• Importin beta-type transport receptors mediate the vast majority of transport pathways between cell nucleus and cytoplasm [4].

Biological context of Fs(2)Ket

• Together, these data indicate that DIM-7 and Ketel are components of the nuclear import machinery for activated D-ERK [5].
• The Ketel(+) transgenes slightly reduce effects of the Ketel(D) mutations [6].
• The Ketel gene is not expressed in most larval tissues, as revealed by the expression pattern of a Ketel promoter-lacZ reporter gene [6].
• Notably, the P446L mutant importin-beta does not exert its dominant-negative effect on nuclear protein import and has no effect on mitotic spindle-related functions and chromosome segregation [7].
• The axon guidance and cell adhesion defects are both due to a disruption in the function of Ketel, the Drosophila ortholog of Importinbeta [8].

Anatomical context of Fs(2)Ket

• However, it interferes with nuclear envelope formation during mitosis-to-interphase transition, revealing a novel function of importin-beta [7].
• Indeed, Ketel supports import of appropriately designed substrates into nuclei of digitonin-permeabilized HeLa cells [1].
• As shown by a polyclonal anti-Ketel antibody, nurse cells synthesize and transfer Ketel protein into the oocyte cytoplasm from stage 11 of oogenesis [1].

Other interactions of Fs(2)Ket

• The Ketel(D) dominant female-sterile mutations and their ketel(r) revertant alleles identify the Ketel gene, which encodes the importin-beta (karyopherin-beta) homologue of Drosophila melanogaster [6].

Analytical, diagnostic and therapeutic context of Fs(2)Ket

• Western blot analysis revealed that the Ketel gene is not expressed in several larval cell types of late third instar larvae [1].

References