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A prion-like domain of TFEB mediates the co-aggregation of TFEB and mHTT.

Authors :
Yang, Junsheng
Xu, Huilin
Zhang, Chaoyue
Yang, Xiaotong
Cai, Weijie
Chen, Xiaoli
Source :
Autophagy; Feb2023, Vol. 19 Issue 2, p544-550, 7p
Publication Year :
2023

Abstract

The aggregation of mutant HTT (huntingtin; mHTT) is a hallmark of Huntington disease (HD). mHTT aggregates interact and sequester dozens of proteins and affect diverse key cellular functions. Here we report that TFEB (transcription factor EB), a master regulator of lysosome biogenesis and autophagy, is yet another protein that co-aggregates with mHTT. We also found the mHTT-TFEB co-aggregation is mediated by a prion-like domain (PrLD) near the N terminus of TFEB. Our findings point out a possible limitation for therapeutic strategies targeting TFEB to clear mHTT, and also provided a possible explanation for controversies that TFEB overexpression lowered soluble mHTT in some HD models but failed to reduce mHTT aggregates or HD pathology in others. Moreover, we found that TFE3, another MiT family transcription factor that shares overlapping functions with TFEB, lacks PrLD and does not co-aggregate with mHTT, and thus might serve as an alternative drug target for HD. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15548627
Volume :
19
Issue :
2
Database :
Complementary Index
Journal :
Autophagy
Publication Type :
Academic Journal
Accession number :
161394189
Full Text :
https://doi.org/10.1080/15548627.2022.2083857