Disease relevance of COL4A3BP

• GPBP expression is, in turn, up-regulated in the striated muscle of a Goodpasture patient and in other autoimmune conditions including cutaneous lupus erythematosus, pemphigoid, and lichen planus [1].
• The longest PAE and CERT values were obtained after exposing the E. coli strains to 100 x MIC cefaclor with mean values of 4.07 and 4.87 h, respectively [2].
• The effects of the morphological response of Enterobacteriaceae to cephalosporins on PAE and CERT [2].

High impact information on COL4A3BP

• There have been recent advances in the study of lipid transfer proteins, such as ceramide transfer protein (CERT) and homologues of oxysterol binding protein (OSBP) [3].
• Here, we show that OSBP regulation of SM synthesis involves the endoplasmic reticulum (ER)-to-Golgi ceramide transport protein (CERT) [4].
• Whereas mutations of neither the FFAT motif nor the PH domain inhibited the ceramide transfer activity of CERT in a cell-free system, they impaired the ER-to-Golgi transport of ceramide in intact and in semi-intact cells at near endogenous expression levels [5].
• RNA interference (RNAi) experiments in Chinese hamster ovary (CHO)-K1 cells revealed that OSBP and vesicle-associated membrane protein-associated protein (VAP) were required for stimulation of CERT-dependent ceramide transport and SM synthesis by 25-hydroxycholesterol and cholesterol depletion in response to cyclodextrin [4].
• Regulation of CERT by OSBP, sterols, and VAP reveals a novel mechanism for integrating sterol regulatory signals with ceramide transport and SM synthesis in the Golgi apparatus [4].

Biological context of COL4A3BP

• In human tissues, GPBP shows a more limited expression than GPBPDelta26 but displays a remarkable preference for the small vessels and for histological structures targeted by natural autoimmune responses including alveolar and glomerular basement membranes, the two main targets in Goodpasture disease [1].
• We have recently cloned from a HeLa-derived cDNA library a novel serine/threonine kinase (Goodpasture antigen-binding protein (GPBP)) that phosphorylates the N-terminal region of the human domain (Raya, A. Revert, F, Navarro, S. and Saus J. (1999) J. Biol. Chem. 274, 12642-12649) [1].
• CERT expressed in LY-A cells has an amino acid substitution that destroys its PtdIns4P-binding activity, thereby impairing its Golgi-targeting function [6].

Anatomical context of COL4A3BP

• The recently identified ceramide transfer protein, CERT, is responsible for the bulk of ceramide transport from the endoplasmic reticulum (ER) to the Golgi [7].
• Children with ECC at their initial examination (N = 58) had a 93.0% cert rate, a 67.2% CERT rate and a 60.3% CERT in first molars rate by their last dental examination [8].

Associations of COL4A3BP with chemical compounds

• We show here that the pre-mRNA of GPBP is alternatively spliced in human tissues and that the most common transcript found encodes GPBPDelta26, a molecular isoform devoid of a 26-residue serine-rich motif [1].
• The main pathway of endoplasmic reticulum-to-Golgi transport of ceramide is mediated by CERT, a cytosolic 68-kDa protein, in a nonvesicular manner [9].
• CERT did not mediate the transfer of sphingosine or sphingomyelin at all [9].
• CERT, which is identical to a splicing variant of Goodpasture antigen-binding protein, is a cytoplasmic protein with a phosphatidylinositol-4-monophosphate-binding (PtdIns4P) domain and a putative domain for catalysing lipid transfer [6].
• CERT has a C-terminal START domain for ceramide binding and an N-terminal pleck-strin homology domain that binds phosphatidylinositol 4-phosphate suggesting that phosphatidylinositol (PI) 4-kinases are involved in the regulation of CERT-mediated ceramide transport [7].

Other interactions of COL4A3BP

• A human-specific TNF-responsive promoter for Goodpasture antigen-binding protein [10].

Analytical, diagnostic and therapeutic context of COL4A3BP

• Here we report the molecular cloning of GPBP (Goodpasture antigen-binding protein), a previously unknown 624-residue polypeptide [11].
• It has been shown that the addition of concurrent chemotherapy to radiotherapy (chemoradiotherapy, CRT, or chemotherapy-enhanced radiation therapy, CERT) results in improved clinical outcome in terms of both locoregional control and overall survival in some groups of patients [12].

References