Cancers, Vol. 11, Pages 1600: Mutational Landscape of the BAP1 Locus Reveals an Intrinsic Control to Regulate the miRNA Network and the Binding of Protein Complexes in Uveal Melanoma

Cancers, Vol. 11, Pages 1600: Mutational Landscape of the BAP1 Locus Reveals an Intrinsic Control to Regulate the miRNA Network and the Binding of Protein Complexes in Uveal Melanoma Cancers doi: 10.3390/cancers11101600 Authors: Amit Sharma Arijit Biswas Hongde Liu Sagnik Sen Anoosha Paruchuri Panagiotis Katsonis Olivier Lichtarge Tikam Chand Dakal Ujjwal Maulik M. Michael Gromiha Sanghamitra Bandyopadhyay Michael Ludwig Frank G. Holz Karin U. Loeffler Martina C. Herwig-Carl The BAP1 (BRCA1-associated protein 1) gene is associated with a variety of human cancers. With its gene product being a nuclear ubiquitin carboxy-terminal hydrolase with deubiquitinase activity, BAP1 acts as a tumor suppressor gene with potential pleiotropic effects in multiple tumor types. Herein, we focused specifically on uveal melanoma (UM) in which BAP1 mutations are associated with a metastasizing phenotype and decreased survival rates. We identified the ubiquitin carboxyl hydrolase (UCH) domain as a major hotspot region for the pathogenic mutations with a high evolutionary action (EA) score. This also includes the mutations at conserved catalytic sites and the ones overlapping with the phosphorylation residues. Computational protein interaction studies revealed that distant BAP1-associated protein complexes (FOXK2, ASXL1, BARD1, BRCA1) could be directly impacted by this mutation paradigm. We also described the conformational transition related to BAP1-BRCA-BARD1 ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research