2008;409:471C479. and tyrosinase appearance in melanocytic cells. Over-expression of DGK elevated tyrosinase protein amounts, but didn’t boost tyrosinase mRNA amounts. Glycosidase digestion uncovered that inhibition of DGK decreased only the older type of tyrosinase as well as the loss of tyrosinase caused by DGK inhibition could possibly be blocked partly by protease inhibitors. These total outcomes claim that DGK regulates melanogenesis via modulation from the post-translational digesting of tyrosinase, which might be related to the protein degradation equipment. et al.et al.beliefs were calculated using Learners check, and a < 0.05 is Clarithromycin known as significant. Supplementary Materials Supplementary MaterialClick right here to see.(214K, pdf) ACKNOWLEDGEMENTS We thank Dr. Hideya Ando for useful discussion of the manuscript. This analysis was supported partly with the Intramural Analysis Program from the Country wide Cancer Institute on the National Institutes of Health. Abbreviations DAGdiacylglycerolDGKdiacylglycerol kinaseERendoplasmic reticulumERKextracellular signal-regulated kinaseMAPKmitogen-activated protein kinaseNHEMsnormal human epidermal melanocytesPAphosphatidic acidPKCprotein kinase CUVRultraviolet radiation Footnotes CONFLICT OF INTEREST The authors state no conflict of interest. REFERENCES Allan AE, Archambault M, Messana E, et al. Topically applied diacylglycerols increase pigmentation in guinea pig skin. J Invest Dermatol. 1995;105:687C692. [PubMed] [Google Scholar]Ando H, Kondoh H, Ichihashi M, et al. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J Invest Dermatol. 2007;127:751C761. [PubMed] [Google Scholar]Ando H, Watabe H, Valencia JC, et al. Fatty acids regulate pigmentation via proteasomal degradation of tyrosinase - a new aspect of ubiquitin-proteasome function. J Biol Chem. 2004;279:15427C15433. [PubMed] [Google Scholar]Ando H, Wen Z-M, Kim H-Y, et al. Intracellular composition of fatty acid affects the processing and function of tyrosinase through the ubiquitin-proteasome pathway. Biochem J. 2006;394:43C50. [PMC free article] [PubMed] [Google Scholar]Avila-Flores A, Santos T, Rincon E, et al. Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid. J Biol Chem. 2005;280:10091C10099. [PubMed] [Google Scholar]Bellei B, Maresca V, Flori E, et al. p38 regulates pigmentation via proteasomal degradation of tyrosinase. J Biol Chem. 2010;285:7288C7299. [PMC free article] [PubMed] [Google Scholar]Bertolotto C, Bille K, Ortonne JP, et al. In B16 melanoma cells, the inhibition of melanogenesis by TPA results from PKC activation and diminution of microphthalmia binding to the M-box of the tyrosinase promoter. Oncogene. 1998;16:1665C1670. Clarithromycin [PubMed] [Google Scholar]Blumberg PM, Kedei N, Lewin NE, et al. Wealth of opportunity - the C1 domain as a target for drug development. Curr Drug Targets. 2008;9:641C652. [PMC free article] [PubMed] [Google Scholar]Carsberg CJ, Ohanian J, Friedmann PS. Ultraviolet radiation stimulates a biphasic pattern of 1 1,2-diacylglycerol formation in cultured human melanocytes and keratinocytes by activation of phospholipases C and D. Rabbit Polyclonal to MAP9 Biochem J. 1995;305:471C477. [PMC free article] [PubMed] [Google Scholar]Carsberg CJ, Warenius HM, Friedmann PS. Ultraviolet radiation-induced melanogenesis in human melanocytes. Effects of modulating protein kinase C. J Cell Sci. 1994;107:2591C2597. [PubMed] [Google Scholar]Chibalin AV, Leng Y, Vieira E, et al. Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance. Cell. 2008;132:375C386. [PubMed] [Google Scholar]Ding L, Bunting M, Topham MK, et al. Alternative splicing of the human diacylglycerol kinase zeta gene in muscle. Proc Natl Acad Sci U S A. 1997;94:5519C5524. [PMC free article] [PubMed] [Google Scholar]Du X, Jiang Y, Qian W, et al. Fatty acids inhibit growth-factor-induced diacylglycerol kinase alpha activation in vascular smooth-muscle cells. Biochem J. 2001;357:275C282. [PMC free article] [PubMed] [Google Scholar]Gordon PR, Gilchrest BA. Human melanogenesis is stimulated by diacylglycerol. J Invest Dermatol. 1989;93:700C702. [PubMed] [Google Scholar]Halaban R, Cheng E, Zhang Y, et al. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proc Natl Acad Sci USA. 1997;94:6210C6215. [PMC free article] [PubMed] [Google Scholar]Halaban R, Svedine S, Cheng E, et al. Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Proc Natl Acad Sci USA. 2000;97:5889C5894. [PMC free article] [PubMed] [Google Scholar]Hall AM, Orlow SJ. Degradation Clarithromycin of tyrosinase induced by phenylthiourea occurs following Golgi maturation. Pigment Cell Res. 2005;18:122C129. [PubMed] [Google Scholar]Haucke V, Di PG. Lipids and lipid modifications in the regulation of membrane traffic. Curr Opin Cell Biol. 2007;19:426C435. [PMC free article] [PubMed] [Google Scholar]Hemesath TJ, Price ER, Takemoto C, et al. MAP kinase links the.