DHHC20: a human palmitoyl acyltransferase that causes cellular transformation

Abstract

Palmitoylation is required for the activities of several cancer-associated proteins, making the palmitoyl acyltransferase (PAT) enzymes that catalyze these reactions potential targets for anticancer therapeutics. In this study, we sought to identify and characterize a human PAT with activity toward N-terminally myristoylated and palmitoylated proteins. NIH/3t3 cells were stably transfected with vectors containing no insert, wild type human DHHC20, or a serine-substituted DHHS20 mutant. Compared with control cells, cells overexpressing wild-type DHHC20 displayed an increase in palmitoylation activity toward a peptide that mimics the N-terminus of myristoylated and palmitoylated proteins, but had no change in activity toward a peptide that mimics the C-terminus of farnesylated and palmitoylated proteins. Cells expressing DHHS20 had no significant change in activity toward either peptide. Overexpression of DHHC20 also caused phenotypic changes consistent with cellular transformation, including colony formation in soft agar, decreased contact inhibition of growth, and increased proliferation under low-serum conditions. Quantitative polymerase chain reaction analyses of human tissues demonstrated that DHHC20 is expressed in a tissue-specific manner, and is overexpressed in several types of human tumors, including ovarian, breast and prostate. Overall, these results demonstrate that DHHC20 is a human N-terminal-myristoyl-directed PAT involved in cellular transformation, that may play a role in cancer.

Keywords::

• DHHC
• myristoyl
• palmitoyl acyltransferase
• palmitoylation
• proliferation

Acknowledgements

We would also like to thank Dr Zuping Xia for his work synthesizing the peptides used in the IVP assays, and Dr Carola Neumann for her help in conducting the soft agar assays.

Declaration of interest: Financial support was provided by National Institutes of Health Grant 2 RO1 CA075248 (CDS). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.