Two Splice Variants of Y Chromosome-Located Lysine-Specific Demethylase 5D Have Distinct Function in Prostate Cancer Cell Line (DU-145).

One of the major objectives of the Human Y Chromosome Proteome Project is to characterize sets of proteins encoded from the human Y chromosome. Lysine (K)-specific demethylase 5D (KDM5D) is located on the AZFb region of the Y chromosome and encodes a JmjC-domain-containing protein.

KDM5D, the least well-documented member of the KDM5 family, is capable of demethylating di- and trimethyl H3K4. In this study, we detected two novel splice variants of KDM5D with lengths of 2650bp and 2400bp that correspond to the 100 and 80 kDa proteins in the human prostate cancer cell line, DU-145. The knockdown of two variants using the short interfering RNA (siRNA) approach increased the growth rate of prostate cancer cells and reduced cell apoptosis. To explore the proteome pattern of the cells after KDM5D downregulation, we applied a shotgun label-free quantitative proteomics approach. Of 820 proteins present in all four replicates of two treatments, the abundance of 209 proteins changed significantly in response to KDM5D suppression. Of these, there were 102 proteins observed to be less abundant and 107 more abundant in KDM5D knockdown cells compared with control cells. The results revealed that KDM5D knockdown altered the abundance of proteins involved in RNA processing, protein synthesis, apoptosis, the cell cycle, and growth and proliferation. In conjunction, these results provided new insights into the function of KDM5D and its splice variants. The proteomics data are available at PRIDE with ProteomeXchange identifier PXD000416.

Journal of proteome research. 2015 Aug 10 [Epub]

Zohreh Jangravi, Mehdi Sharif Tabar, Mehdi Mirzaei, Pouria Parsamatin, Haghighat Vakilian, Mehdi Alikhani, Mohammad Shabani, Paul A Haynes, Ann K Goodchild, Hamid Gourabi, Hossein Baharvand, Ghasem Hosseini Salekdeh

Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran. , Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran. , The Australian School of Advanced Medicine, Faculty of Human Sciences, Macquarie University , Sydney, New South Wales 2109, Australia. , Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran. , Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran. , Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran. , Biochemistry Department, Iran University of Medical Sciences , Tehran, Iran. , Department of Chemistry and Biomolecular Sciences, Macquarie University , Sydney, New South Wales 2109, Australia. , The Australian School of Advanced Medicine, Faculty of Human Sciences, Macquarie University , Sydney, New South Wales 2109, Australia. , Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR , Tehran, Iran. , Department of Developmental Biology, University of Science and Culture, ACECR , Tehran, Iran. , Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.

PubMed