Abstract
B-cell receptor-associated protein 31 (Bap31) is a three trans-membrane protein of the endoplasmic reticulum (ER). Patients who have loss of function of Bap31 suffered from X-linked syndrome, such as motor and intellectual disabilities, dystonia, and sensorineural deafness. However, the underlying mechanism of Bap31 on X-linked syndrome remains unclear. Here, we found that a total of 21 proteins (9 up-regulated and 12 down-regulated proteins) related with X-linked syndrome were screened from shRNA-Bap31 transfected cells with the isobaric tags for relative and absolute quantification (iTRAQ) technique. One gene with the greatest change trend, monoamine oxidase A (MAOA), was identified. MAOA expression was up-regulated by Bap31 knockdown. However, Bap31 did not affect the ubiquitination degradation of MAOA protein. Of note, Bap31 selectively regulated the expression of cell division cycle associated 7-like (R1/RAM2/CDCA7L/JPO2, a transcriptional repressor of MAOA) and the binding activity of R1 with MAOA promoter, thereby affecting MAOA expression. This study demonstrates the molecular mechanisms of Bap31 in MAOA via R1 and supports the potential function of Bap31 on X-linked syndrome.
Highlights
B-cell receptor-associated protein 31 (Bap31) gene is located from 153,700,492 to 153,724,746 bp on the long (q) arm of the X chromosome in humans (Adachi et al, 1996)
Real-time polymerase chain reaction (PCR) and Western blot were used to analyze the knockdown efficiency of Bap31; the mRNA and protein levels of Bap31 were significantly decreased by 79 and 80% compared with that of the control cells, respectively (Figures 1A,B)
These results demonstrate that the shRNA-Bap31 transfected cells are qualified as Bap31 effectively knockdown cells
Summary
B-cell receptor-associated protein 31 (Bap31) gene is located from 153,700,492 to 153,724,746 bp on the long (q) arm of the X chromosome in humans (Adachi et al, 1996). Bap is evolutionarily conserved and is known as Yet3p in yeast (Wilson and Barlowe, 2010). It transports certain membrane proteins from the ER to other cellular components, such as cellubrevin (Annaert et al, 1997), CD11b/CD18 (Zen et al, 2004), Bap Regulates MAOA by R1. Our former study demonstrates that Bap regulates one of the central nervous system disease-related gene (valosin-containing protein, VCP) expression (Jia et al, 2018). Mutations in Bap induce a severe X-linked phenotype, such as dystonia, deafness, and central hypomyelination (Cacciagli et al, 2013)
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