HACE1 co-localizes with mTOR and RAC1, resulting in RAC1-dependent loss of mTOR protein stability. Together, our data demonstrate that HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, revealing a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.
1 year ago
Journal
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KRAS (KRAS proto-oncogene GTPase) • RAC1 (Rac Family Small GTPase 1) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
An inverse relationship was observed between HACE1 and HIF1α levels in tumors compared to patient-matched normal kidney tissues, highlighting the potential pathophysiological significance of our findings. Together, our data uncover a previously unrecognized function for the HACE1 tumor suppressor in blocking HIF1α accumulation under hypoxia in a RAC1-dependent manner.
almost 4 years ago
Journal
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KRAS (KRAS proto-oncogene GTPase) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • RAC1 (Rac Family Small GTPase 1)