AI Article Synopsis
- * Proteomic studies reveal that additional partners of R2TP, like the Tuberous Sclerosis Complex (TSC), interact through specific domains, indicating a more extensive network of protein interactions.
- * The findings suggest that R2TP aids in the recruitment of TSC1 and TSC2 via different pathways, and the activity of RUVBL1/2 ATPases is essential for their proper assembly, indicating a complex regulatory mechanism.
Article Abstract
The R2TP chaperone is composed of the RUVBL1/RUVBL2 AAA+ ATPases and two adapter proteins, RPAP3 and PIH1D1. Together with HSP90, it functions in the assembly of macromolecular complexes that are often involved in cell proliferation. Here, proteomic experiments using the isolated PIH domain reveals additional R2TP partners, including the Tuberous Sclerosis Complex (TSC) and many transcriptional complexes. The TSC is a key regulator of mTORC1 and is composed of TSC1, TSC2 and TBC1D7. We show a direct interaction of TSC1 with the PIH phospho-binding domain of PIH1D1, which is, surprisingly, phosphorylation independent. Via the use of mutants and KO cell lines, we observe that TSC2 makes independent interactions with HSP90 and the TPR domains of RPAP3. Moreover, inactivation of PIH1D1 or the RUVBL1/2 ATPase activity inhibits the association of TSC1 with TSC2. Taken together, these data suggest a model in which the R2TP recruits TSC1 via PIH1D1 and TSC2 via RPAP3 and HSP90, and use the chaperone-like activities of RUVBL1/2 to stimulate their assembly.
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| http://dx.doi.org/10.1016/j.jmb.2024.168840 | DOI Listing |
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