Disease relevance of TRPC4AP

• Loss of interferon-gamma inducibility of TAP1 and LMP2 in a renal cell carcinoma cell line [1].
• Normal brain tissue and glioma tissue specimens also showed undetectable levels of TAP1 protein and the same levels of LMP2 protein as lymphoblastoid B cells [2].
• TAP1 expression was significantly associated with regression of melanoma lesions, since the staining pattern with anti-TAP1 antibody was positive in 38 of the 39 lesions exhibiting regression phenomena and in only 24 of the 35 lesions without histopathological signs of tumour regression [3].

High impact information on TRPC4AP

• The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region [4].
• The effects of IFN-gamma on TAP1 and LMP2 expression revealed a loss of up-regulation in Caki-2 cells, but not in Caki-1 cells [1].
• Catalytic Site Modifications of TAP1 and TAP2 and Their Functional Consequences [5].
• By using an in vitro expression system we demonstrate that the biogenesis of functional TAP depends on the assembly of preexisting TAP1 with newly synthesized TAP2, but not vice versa [6].
• Thus, the naturally occurring Asp(668) and Gln(701) alterations of TAP1 are likely to contribute to attenuated catalytic activity at the first nucleotide binding site (the TAP1 site) of TAP complexes [5].

Biological context of TRPC4AP

• The transporter associated with antigen processing (TAP) comprises two structurally related subunits, TAP1 and TAP2, that form stable complexes in endoplasmic reticulum (ER) membranes [7].
• In this study, TAP1 and TAP2 alleles were identified in homozygous typing cell (HTC) lines, allowing resolution of specific haplotypes in conjunction with the highly polymorphic HLA class II region haplotypes [8].
• Stable cell surface presentation of HLA class I molecules requires active transport of antigenic peptides across the endoplasmic reticulum by products of two genes, TAP1 and TAP2, which map in the major histocompatibility complex class II region [8].
• Further, association analyses using four polymorphic microsatellite markers located around the TAP1 and TNFA genes were also carried out [9].
• Biogenesis of functional antigenic peptide transporter TAP requires assembly of pre-existing TAP1 with newly synthesized TAP2 [6].

Anatomical context of TRPC4AP

• In this study we report that IFN-gamma and thrombopoietin (TPO) strongly increase TAP1 protein expression in megakaryocytes, followed by an enhanced expression of MHC(I) on the cell surface [10].
• Although Tap-1 protein was detectable in extravillous cytotrophoblast cells (chorionic cytotrophoblast cells) as expected, HLA class I negative syncytiotrophoblast contained low intensity hybridization and immunostaining signals [11].

Associations of TRPC4AP with chemical compounds

• Compared with other ABC transporters, the first nucleotide binding site contains non-consensus catalytic site residues, including Asp(668) in the Walker B region of TAP1 (in place of a highly conserved glutamic acid), and Gln(701) in the switch region of TAP1 (in place of a highly conserved histidine) [5].

Regulatory relationships of TRPC4AP

• Further, a dominant-inhibitory mutant of TRUSS inhibited TNF-alpha-induced AP-1 activation [12].

Other interactions of TRPC4AP

• The impaired TAP1 protein expression was associated with deficient TAP2 protein expression, peptide binding, translocation, and MHC class I surface expression [13].
• CONCLUSIONS: Tunisian persons carrying the glycine-637 of the TAP1 protein may have an increased risk of atopy [14].

Analytical, diagnostic and therapeutic context of TRPC4AP

• In situ hybridization data demonstrate that tap1 is expressed in the tapetum of the anthers and fil1 in the filament of the stamen and at the bases of the petals [15].

References