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bioRxiv · 10.64898/2026.08.14.742015

TBC-2, a Rab GTPase activating protein, regulates the localization of the HLH-30/TFEB and PQM-1 transcription factors in the C. elegans intestine

Saha, S.·Meras, I.·Rocheleau, C. E.
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Abstract

Insulin/IGF signaling (IIS) inhibits the nuclear localization of the DAF-16/FOXO transcription factor to regulate longevity and stress resistance in C. elegans. In the intestine, IIS promotes DAF-16 localization to endosomes and loss of TBC-2, a RAB-5 GAP, results in increased endomembrane localization of DAF-16 at the expense of nuclear localization, decreased DAF-16 target gene expression, longevity and stress resistance. Here we found that TBC-2 differentially regulates the localization of the IIS-regulated transcription factors PQM-1 and HLH-30/TFEB. Our results suggest a broader role for TBC-2 in negatively regulating IIS and that TBC-2 likely functions at an upstream point in the IIS pathway.

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Saha, S., Meras, I., Rocheleau, C. E.. 2026-08-21. TBC-2, a Rab GTPase activating protein, regulates the localization of the HLH-30/TFEB and PQM-1 transcription factors in the C. elegans intestine. https://doi.org/10.64898/2026.08.14.742015

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