B-Cell Receptor-Associated Protein 31 Negatively Regulates the Expression of Monoamine Oxidase A Via R1

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.

α-Synuclein Up-regulates Monoamine Oxidase A Expression and Activity via Trans-Acting Transcription Factor 1

“…To explore the mechanism of α-SYN on MAOA expression, we detected the co-localization of α-SYN and MAOA and the data revealed that there was no direct interaction between α-SYN and MAOA, which is consistent with previous findings (Kang et al, 2018 ). Our previous study and others showed that MAOA was degraded in vitro with the presence of a protein synthesis inhibitor (Jiang et al, 2006 ; Jia et al, 2020b ). Kabayama et al found that RING finger-type E3 ubiquitin ligase Rines/RNF180 increased the ubiquitination and degradation of MAOA (Kabayama et al, 2013 ).…”

“…Total RNA was extracted and used to synthesize cDNA according to the manufacturer’s instructions (TransGen Biotechnology, Beijing, China). The primers sequences and analysis methods used in the present study were described previously (Jia et al, 2020a , b ).…”

“…N2a/α-SYN and N2a control cells were co-transfected with MAOA promoter fragment luciferase reporter plasmid (0.5 μg) and phRL-SV40 vector (0.05 μg) using lipofectamine 6000 (Beyotime) for 48 h according to our precious protocol (Jia et al, 2020b ). Cells were sonicated in lysis buffer and then centrifuged for 10 min at 12,000× g to get the supernatant.…”

“…The obtained complexes were purified with a DNA purification kit (Beyotime) and then detected with Real-time PCR. The methods of analyzed values were described previously (Jia et al, 2020a , b ).…”

A-Syn(ful) MAM: A Fresh Perspective on a Converging Domain in Parkinson’s Disease

“…Interestingly, deficiency of BAP31 has been found to contribute to the formation of amyloid-beta plaques in Alzheimer’s disease (AD) [ 176 ]. Furthermore, with particular relevance to PD, BAP31 negatively regulates the expression of monoamine oxidase A (MAO-A), the enzyme that degrades monoamine neurotransmitters, such as dopamine, via cell division cycle-associated 7-like (R1/RAM2/CDCA7L/JPO2, a transcriptional repressor of MAOA) [ 177 ].…”