PAX5 is the transcriptional activator of mucolipin-2 (MCOLN2) gene.

Abstract

Transient receptor potential mucolipin (TRPML) proteins belong to the TRP superfamily of non-selective cation channels. The TRPML1, -2, and -3 proteins are encoded by Mucolipin (MCOLN)-1, -2 and -3 genes, respectively. TRPML1 has been associated with mucolipidosis type IV (MLIV), while no disease phenotype has been linked with TRPML2 or -3 protein. The TRPML proteins share high sequence similarities, form hetero-tetramers, and serve in membrane trafficking, autophagy, and metal homeostasis. Previous studies suggest that TRPML2 serves a role in the immune system; however, the evidence is mostly indirect. We hypothesize that if TRPML2 is involved in immune function its expression would be likely regulated by an immune-associated transcription factor protein. Thus, we set out to identify the core promoter region and the transcription factor responsible for MCOLN2 gene expression. Using dual-luciferase assay and over-expression analyses, we reveal for the first time that B-cell lineage specific activator protein (BSAP), also known as paired box 5 (PAX5), controls MCOLN2 expression. Specifically, heterologous expression of PAX5 in HEK-293 cells significantly increased endogenous MCOLN2 transcript and TRPML2 protein levels, while RNA interference targeting endogenous PAX5 reduced its effect. Site-directed mutagenesis studies showed that the core promoter and PAX5 binding region to be between -79 and -60 base pairs upstream of the transcriptional start site. Thus, our findings add to a growing list of evidence for TRPML2's possible involvement in the immune system. The knowledge gained from this study could be used to further characterize the role of TRPML2 in B-cell development and function.

• Authors: Jessica A Valadez, Math P Cuajungco
• Journal: Gene (Gene) Vol. 555 Issue 2 Pg. 194-202 (Jan 25 2015) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 25445271 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Mcoln2 protein, human
• PAX5 Transcription Factor
• PAX5 protein, human
• Transcription Factors
• Transient Receptor Potential Channels

Topics

• B-Lymphocytes (metabolism)
• Cell Line, Tumor
• Chromosome Mapping
• CpG Islands
• Endosomes (metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Homeostasis
• Humans
• Lysosomes (metabolism)
• Mutagenesis, Site-Directed
• PAX5 Transcription Factor (metabolism)
• Phenotype
• Promoter Regions, Genetic
• Protein Binding
• RNA Interference
• Transcription Factors (metabolism)
• Transient Receptor Potential Channels (metabolism)