Disease relevance of ITGB4BP

• Overexpression of p27BBP in head and neck carcinomas and their lymph node metastases [1].
• In particular, p27BBP increased progressively from adenomas to carcinomas and, in the latter, was related to the tumor stage [2].
• Expression of a highly conserved protein, p27BBP, during the progression of human colorectal cancer [2].

High impact information on ITGB4BP

• Surprisingly, in the absence and in the presence of the beta4 integrin subunit, p27(BBP/eIF6) is in the nucleolus and associated with the nuclear matrix [3].
• The data obtained in vivo suggest an evolutionarily conserved function of p27(BBP/eIF6) in ribosome biogenesis or assembly rather than in translation [3].
• In epithelial cells containing beta4 integrin, p27(BBP/eIF6) is present in the cytoplasm and enriched at hemidesmosomes with a pattern similar to that of beta4 integrin [3].
• The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly [3].
• Phosphorylation of mammalian eukaryotic translation initiation factor 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that phosphorylation of Tif6p regulates its nucleocytoplasmic distribution and is required for yeast cell growth [4].

Biological context of ITGB4BP

• Taken together, these data show that ITGB4BP gene expression is highly regulated in vivo, possibly by the combination of tissue specific factors and protein synthesis pathways [5].
• Localization of p27 beta 4 binding protein gene (ITGB4BP) to human chromosome region 20q11.2 [6].
• PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue [7].
• In vitro and in vivo studies demonstrated that p27BBP is essential for cell viability and has a primary function in the biogenesis of the 60S ribosomal subunit [5].
• Functional analysis of GABP consensus sequences by point mutations, EMSA (electrophoretic mobility shift assay) and a dominant negative mutant indicates that GABP is essential for eIF6 promoter activity [8].

Anatomical context of ITGB4BP

• Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly [7].
• In the present work, we have isolated a protein kinase from rabbit reticulocyte lysates on the basis of its ability to phosphorylate recombinant human eIF6 [4].
• In cultured cells, p27BBP mRNA and protein are constitutively expressed and stable [5].
• The aim of this study was to investigate the distribution of p27BBP in gut epithelium and its behavior during progression of human colorectal carcinomas [2].
• We also found that there was enhanced eIF-6 expression in mast cells stimulated with PMA plus calcium ionophore [9].

Associations of ITGB4BP with chemical compounds

• p27(BBP/eIF6) is an evolutionarily conserved protein that was originally identified as p27(BBP), an interactor of the cytoplasmic domain of integrin beta4 and, independently, as the putative translation initiation factor eIF6 [3].
• Eukaryotic translation initiation factor-6 enhances histamine and IL-2 production in mast cells [9].
• A wheat germ ribosome dissociation factor, eukaryotic initiation factor 6 (eIF-6), has been purified almost to homogeneity from the 25 to 40% ammonium sulfate fraction of the postribosomal supernatant [10].
• The increase in eIF-6 gene expression in murine mast cells was blocked by therapeutic agents such as dexamethasone and cyclosporin A [9].

Physical interactions of ITGB4BP

• Furthermore, eIF6 interacts in the cytoplasm with RACK1, a receptor for activated protein kinase C (PKC) [7].

Other interactions of ITGB4BP

• We propose that eIF6 release regulates subunit joining, and that RACK1 provides a physical and functional link between PKC signalling and ribosome activation [7].

Analytical, diagnostic and therapeutic context of ITGB4BP

• Western blotting confirmed increased p27BBP in dysplastic adenomas and in carcinomas [2].
• We also demonstrate, by immunogold electron microscopy with an indirect immunoreaction technique on ultrathin sections of human skin and Sepia integument, that p27BBP is constantly present in both species in epithelial cells, fibroblasts, and muscle fibers [11].

References