Disease relevance of Skp1a

• The abundant and almost exclusive expression of OCP-II protein in the mammalian cochlea has fuelled speculation that mutations in the OCP2 gene may result in inherited forms of hearing impairment [1].

High impact information on Skp1a

• Purified centrosomes also contain Skp1, and Cul1 modified by the ubiquitin-like molecule NEDD8, suggesting a role for NEDD8 in targeting [2].
• Using an in vitro assay for centriole separation in Xenopus extracts, antibodies to Skp1 or Cul1 block separation [2].
• Using immunofluorescence microscopy, we show that in mammalian cells the Skp1 protein and the cullin Cul1 are localized to interphase and mitotic centrosomes and to the cytoplasm and nucleus [2].
• In contrast, Skp1 engages the SIP CS domain exclusively through weak interactions that are not coupled to the other domains [3].
• Through interacting with suppressor of the G2 allele of Skp1 (SGT1) and Hsp90, plant CHORD-containing protein RAR1 (required for Mla resistance 1) plays a critical role in disease resistance mediated by multiple R genes [4].

Biological context of Skp1a

• Tceb1l is highly conserved throughout vertebrates and maps to mouse chromosome 11 and to the syntenic region of human chromosome 5q31 [5].
• Our data suggest that the cytogenetic localisations of these OCP2 related sequences do not correlate with the precise chromosomal positions of deafness loci so far identified [1].
• Biochemical features of major organ of Corti proteins (OCP-I and OCP-II) including partial amino acid sequence [6].
• Two strains of mice (NMRI and C57/BL) were each immunized with a 15kDa recombinant Fasciola hepatica fatty acid binding protein (FABP) (Fh15) and challenged percutaneously with Schistosoma bovis cercariae [7].

Anatomical context of Skp1a

• Tceb1l shows a restricted pattern of expression in the early mouse embryo, where it is absent from the neurectoderm; later Tceb1l is expressed in the caudal region of the neural tube, followed by widespread expression in many tissues, including the brain and spinal cord [5].
• Deconvolution and immunoelectron microscopy suggest that Skp1 forms an extended pericentriolar structure that may function to organize the centrosome [2].
• Further biochemical and biophysical characterization of two low-molecular-weight, strongly acidic proteins that are present at extremely high levels in the organ of Corti, tentatively named OCP-I and OCP-II, is presented [6].
• These cell lines were all positive for the neuroepithelial precursor cell marker nestin and for the inner ear cell marker OCP2 [8].

Other interactions of Skp1a

• SCF ubiquitin ligases, composed of three major subunits, Skp1, Cul1, and one of many F box proteins (Fbps), control the proteolysis of important cellular regulators [9].
• A coimmunoprecipitation assay has revealed the in vivo interaction between Skp1 and Fwd2 through the F-box domain [10].

Analytical, diagnostic and therapeutic context of Skp1a

• Cell fractionation experiments confirmed that macroH2A1 resides at a pericentrosomal location in close proximity to the known centrosomal proteins gamma-tubulin and Skp1 [11].

References