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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
Molecular genomic insights into melanoma associated proteins PRAME and BAP1
Debaleena Nawn1, Sk Sarif Hassan2, Altijana Hromić-Jahjefendić3
1Department of Computer Science and Engineering, Adamas University, Jagannathpur, Kolkata, West Bengal, India.
Abstract:
Melanoma, a globally prevalent skin cancer with over 325,000 new cases annually, necessitates a comprehensive under- standing of its molecular components. This study looks at the PRAME (cutaneous melanoma-associated antigen) and BAP1 (gene controlling gene-environment interactions) proteins. Both PRAME and BAP1 are associated with critical genomic alterations that significantly influence melanoma progression and patient outcomes. PRAME is overexpressed in various cancers, especially uveal melanoma (UM), where high levels correlate with poor prognosis and genomic instability linked to chromosome 8q12 alterations. Meanwhile, mutations in BAP1 contribute to increased genomic instability and a higher risk of metastasis in UM, highlighting its importance as a key prognostic marker in tumorigenesis. Established approaches along with features proposed in this work are used to investigate sequence conservation, polyglutamic acid presence, intrinsic disorder of proteins, polar-nonpolar residues arrangement PRAME and BAP1 conserved residues highlight their critical roles in protein function and interaction. Sequence invariance indicates the possibility of functional relevance and evolutionary conservation. PRAME has enhanced intrinsic disorder and flexibility, whereas BAP1 has changed disorder-promoting residue sequences. Polyglutamic acid strings are found in both proteins, emphasizing their modulatory involvement in protein interactions. The ratios and spatial arrangement of amino acids have a profound influence on interactions and gene dysregulation. This work contributes to a better knowledge of the two melanoma-associated proteins viz. PRAME and BAP1 by unraveling their structural and functional complexities.
Insights
This study reveals critical structural and functional insights into PRAME (cutaneous melanoma-associated antigen) and BAP1 proteins, key players in melanoma progression. Understanding their complexities aids in developing targeted melanoma therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Melanoma is a prevalent skin cancer with significant global impact.
- PRAME and BAP1 proteins are implicated in melanoma development and progression.
- Uveal melanoma (UM) shows specific associations with PRAME overexpression and BAP1 mutations.
Purpose of the Study:
- To investigate the structural and functional characteristics of PRAME and BAP1 in melanoma.
- To explore the roles of sequence conservation, protein disorder, and amino acid composition in protein function.
- To enhance understanding of these proteins' involvement in melanoma tumorigenesis.
Main Methods:
- Analysis of sequence conservation and evolutionary patterns.
- Investigation of polyglutamic acid presence and intrinsic protein disorder.
- Examination of polar-nonpolar amino acid arrangements and spatial distribution.
Main Results:
- Conserved residues in PRAME and BAP1 suggest critical roles in protein function and interactions.
- PRAME exhibits enhanced intrinsic disorder and flexibility.
- BAP1 shows altered disorder-promoting residue sequences, and both proteins contain polyglutamic acid strings.
Conclusions:
- PRAME and BAP1 possess distinct yet complementary structural features influencing their function in melanoma.
- Sequence conservation and amino acid arrangements highlight their evolutionary importance and functional relevance.
- Further understanding of PRAME and BAP1 structural complexities can inform melanoma treatment strategies.

