Abstract
Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the non-synonymous single nucleotide polymorphisms (SNP) 538G > A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC (ATP-binding cassette) transporter in apocrine glands. The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G > A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients’ response to nucleoside-based chemotherapy.
Highlights
ATP-binding cassette (ABC) proteins form one of the largest protein families encoded in the human genome (Dean et al, 2001; Holland et al, 2003)
There is no putative mouse or rat orthologous gene corresponding to human ABCC11 (Shimizu et al, 2003), which indicates that ABCC11 is not an orthologous gene but rather a paralogous gene generated by gene duplication in the human genome
ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION OF THE single nucleotide polymorphisms (SNP) VARIANT OF ABCC11 Why does one SNP (c.538G > A) in the human ABCC11 gene affect the function of apocrine glands? To address this question, we have recently provided evidence that proteasomal degradation of the SNP variant (Arg180) of ABCC11 is the underlying molecular mechanism (Toyoda et al, 2009)
Summary
ATP-binding cassette (ABC) proteins form one of the largest protein families encoded in the human genome (Dean et al, 2001; Holland et al, 2003). Characterization of ABCC11 as a cyclic nucleotide efflux pump In vitro characterization of substrate selectivity of ABCC11 Characterization as an apical efflux pump for steroid sulfates in CNS Identification of ABCC11 SNP c.538G > A as the determinant of human earwax type Association between the degrees of apocrine colostrum secretion and ABCC11 genotype Involvement of ABCC11 in 5-fluorouracil resistance in lung cancer cell line Regulation of ABCC11 expression by estrogen in MCF7 cells Discovery of ubiquitination and proteasomal degradation of SNP c.538G > A variant Association between axillary osmidrosis and ABCC11 wild-type
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