Proteomic analysis identifies novel binding partners of BAP1

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• BRCA1-associated protein 1 (BAP1) is a crucial tumor suppressor linked to various cancers, including mesothelioma and melanoma.
• BAP1 functions as a deubiquitinating enzyme involved in cell growth, DNA repair, and stress responses.
• BAP1 forms complexes with ASXL proteins (PR-DUB) to regulate histone modifications.

Purpose of the Study:

• To identify novel cytoplasmic proteins that interact with BAP1.
• To elucidate new cellular pathways involving BAP1.

Main Methods:

• Utilized GFP-tagged BAP1 expression in an endogenous BAP1-deficient cell line.
• Employed affinity purification followed by mass spectrometry (AP-MS) to detect protein interactions.
• Validated interactions at endogenous levels using specific assays.

Main Results:

• Identified Histone acetyltransferase 1 (HAT1) as a novel BAP1 interacting protein.
• Discovered interactions between BAP1 and all subunits of the heptameric coat protein complex I (COPI).
• Confirmed that COPI interaction with BAP1 does not involve canonical COPI cargo sorting signals.

Conclusions:

• Novel cytoplasmic interactors of BAP1, including HAT1 and COPI, have been identified.
• These findings suggest new roles for BAP1 in cellular processes beyond its known functions.
• The interaction with COPI highlights potential BAP1 involvement in vesicle trafficking pathways.