Disease relevance of ABCC11

• To test whether ABCC11 directly confers 5-fluorouracil (5-FU) resistance, we used the 5-FU-resistant subline PC-6/FU23-26 selected from PC-6 human small-cell lung cancer cells by 5-FU and found that it increases the resistance by approximately 25-fold [1].
• MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer [2].
• A rapid increase in serum levels occurred in response to bacterial infections (MRP8/14 up to 6,230 ng/ml; PCT up to 297 ng/ml) [3].
• The myeloic related protein MRP8/14 (27E10 antigen)--usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function [4].
• In contrast, MRP8 expression is weak or absent in mononuclear phagocytes of sarcoidosis and tuberculosis [5].

Psychiatry related information on ABCC11

• Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis [6].

High impact information on ABCC11

• Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors [7].
• A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome [8].
• Myeloid-related protein 8 (MRP8) and MRP14, S100 proteins secreted by activated phagocytes, bind specifically to endothelial cells [9].
• We demonstrated that the expression of MRP8/MRP14 closely correlated with the inflammatory activity in systemic vasculitis, confirming the important role of these proteins for distinct inflammatory reactions in endothelia [9].
• This phosphorylation inhibits MRP8/MRP14-induced tubulin polymerization [10].

Biological context of ABCC11

• We speculate that the decreased 3TC accumulation in the CEM 3TC might be due to the upregulation of ABCC11 [11].
• Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12 [12].
• In spite of the genes coding for both ABCC11 and ABCC12 being tandemly located on human chromosome 16q12.1, no putative mouse orthologous gene corresponding to the human ABCC11 was detected at the mouse chromosome 8D3 locus [13].
• ABCC11 and ABCC12 genes consist of 30 and 29 exons, respectively, and they are tandemly located in a tail-to-head orientation on human chromosome 16q12 [14].
• By searching cDNA libraries from various human tissues, we have identified alternative splicing variants of ABCC11 and ABCC12 genes at significantly high frequencies [14].

Anatomical context of ABCC11

• Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 microM [15].
• Additionally, ABCC11 was localized to axons of the peripheral nervous system [15].
• The transcripts of ABCC11 and ABCC12 genes were detected by PCR in various adult human tissues, including liver, lung, and kidney, and also in several fetal tissues [14].
• 1. The smaller 4.1-kb transcript of MRP8 is found in testis and may initiate within intron 6 of the gene [2].
• We determined the FN-adhesive capacity and integrin expression of monocytes of type 1 and type 2 diabetic patients and related them to the subjects' serum levels of MRP-8, -14 and -8/14 [16].

Associations of ABCC11 with chemical compounds

• Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11) [17].
• These findings suggest that ABCC11 confers 5-FU resistance in the sublines by enhancing the efflux for the active metabolite FdUMP [1].
• Previously, methotrexate also increased the efflux by ABCC11, and we found cross-resistance to methotrexate in PC-6/FU23-26 cells [1].
• MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine [18].
• Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system [15].

Regulatory relationships of ABCC11

• Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin [16].

Other interactions of ABCC11

• As one of the results of this project, we present two new members of the human ABCC subfamily, ABCC11 and ABCC12 [12].
• Phylogenetic analysis determined that ABCC11 and ABCC12 are derived by duplication, and are most closely related to the ABCC5 gene [12].
• ABCC10, ABCC11, and ABCC12 [19].
• MRP8/ABCC11 directly confers resistance to 5-fluorouracil [1].
• ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction [15].

Analytical, diagnostic and therapeutic context of ABCC11

• Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy [15].
• MRP8/14 levels were measured by ELISA (BMA Biomed), PCT by a sensitive immunoluminiscent assay ILMA (Brahms Diagn.) RESULTS: Both parameters showed very low basal levels in healthy subjects (range 303-1,660 ng/ml of MRP8/14; less than 0.08 ng/ml of PCT) [3].
• Serum PCT concentration remained low in the presence of kidney allograft rejection, where MRP8/14 levels were increased [3].
• An uncomplicated outcome of kidney or heart transplantation did not change basal serum MRP8/14 and PCT levels [3].
• MRP 8/14 and procalcitonin serum levels in organ transplantations [3].

References