This model of prostate cancer is based on the observation that the Drosophila adult male accessory gland acts as a functional homolog of the mammalian prostate. It was hypothesized that normal cell growth and migration of secondary cells in the accessory gland may be regulated by Drosophila orthologs of known regulators of human prostate cancer progression. A number of the genes in this category are highly expressed in the male accessory gland; for several these, knockdown via RNAi was shown to result in changes in the number or migration of the secondary cells. Using RNAi directed against genes highly expressed in the accessory gland and screening for similar phenotypes, additional genes were identified that contribute to the regulation of the growth and migration of accessory gland secondary cells, including MrgBP. Human orthologs of the newly identified genes were shown to promote invasive activity in a human cell-line model of prostate cancer. (FBrf0226167)
There is a single high-scoring ortholog of Dmel\MrgBP in humans, MRGBP (MRG domain binding protein); the protein encoded by MRGBP is a component of a histone acetyltransferase (HAT) complex, which impacts transcriptional regulation by acetylation of nucleosomal histones. The human MRGBP gene has not been introduced into flies.
There are no classical amorphic or loss-of-function mutations available for Dmel\MrgBP. For assessment of function in the accessory gland, RNAi-mediated knockdown of MrgBP was controlled by using a temperature-sensitive driver and targeting newly eclosed, newly mated males. Knockdown of MrgBP results in a decrease in the number of secondary cells compared to controls. Physical interactions of Dmel\MrgBP have been characterized; see below and in the gene report for MrgBP.
[updated Dec. 2016 by FlyBase; FBrf0222196]
Prostate cancer is the most common cancer in American men and is usually very slowly progressive; it is diagnosed in an estimated 80% of men who reach age 80 (http://www.webmd.com/prostate-cancer; 2016.12.20).
The MRGBP-encoded protein is a component of the NuA4 histone acetyltransferase (HAT) complex, which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. [Gene Cards, MRGBP; 2016.12.20]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human MRGBP (1 Drosophila to 1 human). Dmel\MrgBP shares 35% identity and 52% similarity with human MRGBP.
