Roles of TFE3 Fusion Oncoprotein Condensates in Renal Cell Carcinoma
Embargo until
2025-05-01
Date
2022-05-09
Authors
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Publisher
Johns Hopkins University
Abstract
TFE3 fusion Renal Cell Carcinoma is a type of Renal Cell Carcinoma that is caused by genome rearrangements. In TFE3 fusion renal cell carcinoma, the TFE3 transcription factor is fused with other proteins, leading to formation of fusion TFE3 oncoproteins. However, the molecular mechanisms underlying how TFE3 oncoprotein leads to cancer are not well characterized. Here, we demonstrated that TFE3 fusion oncoproteins (SFPQ-TFE3 and NONO-TFE3) form distinct biomolecular condensates inside the nucleus. A subpopulation of these condensates colocalize with paraspeckles, membrane-less organelles that were known to mediate breast cancer progression. The TFE3 fusion oncoprotein condensates have dynamic liquid-like properties. We propose that these condensates function by concentrating transcription related factors to drive TFE3 fusion renal cell carcinoma malignancy.
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Keywords
Biomolecular condensates, TFE3 Renal Cell Carcinoma, Cancer