Identification of ZDHHC14 as a novel human tumour suppressor gene

Abstract

Genomic changes affecting tumour suppressor genes are fundamental to cancer. We applied SNP array analysis to a panel of testicular germ cell tumours to search for novel tumour suppressor genes and identified a frequent small deletion on 6q25.3 affecting just one gene, ZDHHC14. The expression of ZDHHC14, a putative protein palmitoyltransferase with unknown cellular function, was decreased at both RNA and protein levels in testicular germ cell tumours. ZDHHC14 expression was also significantly decreased in a panel of prostate cancer samples and cell lines. In addition to our findings of genetic and protein expression changes in clinical samples, inducible overexpression of ZDHHC14 led to reduced cell viability and increased apoptosis through the classic caspasedependent apoptotic pathway and heterozygous knockout of ZDHHC14 decreased cell colony formation ability. Finally, we confirmed our in vitro findings of the tumour suppressor role of ZDHHC14 in a mouse xenograft model, showing that overexpression of ZDHHC14 inhibits tumourigenesis. Thus, we have identified a novel tumour suppressor gene that is commonly down-regulated in testicular germ cell tumours and prostate cancer, as well as given insight into the cellular functional role of ZDHHC14, a potential protein palmitoyltransferase that may play a key protective role in cancer.

The Canonical DHHC Motif Is Not Absolutely Required for the Activity of the Yeast S-acyltransferases Swf1 and Pfa4

“…There are several examples in the literature where the effects observed upon expression of mutated PATs have been assigned to non-canonical functions of these proteins when there might actually be effects of reduced palmitoylation activity (21,43). It might be advisable to use more than one mutant or combinations of mutations (i.e.…”

Protein post-translational modifications: In silico prediction tools and molecular modeling

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“…The most common approach for detecting prenylation is to use expensive radiolabeling techniques [203], [204]. Initially, the prenylation motif was suggested to be CaaX, i.e.…”

The Characteristics of Mirna Binding Sites in Mrna of Zfhx3 Gene and Its Orthologs

“…With ΔG = -119 kJ/mole and the ΔG/ΔGm value of 90 %, the association of miR-3692-5p with the target gene ZFHX3 could serve as a stroke marker. MicroR-3692-5p was co-expressed with the gene of the ZDHHC14 transcription factor, which is expressed in many tissues as an oncosupressor (Yeste-Velasco et al, 2014).…”