PIH1D1

Last update 08 May 2025

Basic Info

Synonyms

DNAAF14, FLJ20643, MOT48

+ [6]

Introduction

Involved in the assembly of C/D box small nucleolar ribonucleoprotein (snoRNP) particles (PubMed:17636026). Recruits the SWI/SNF complex to the core promoter of rRNA genes and enhances pre-rRNA transcription (PubMed:22368283, PubMed:24036451). Mediates interaction of TELO2 with the R2TP complex which is necessary for the stability of MTOR and SMG1 (PubMed:20864032). Positively regulates the assembly and activity of the mTORC1 complex (PubMed:24036451).

100 Clinical Results associated with PIH1D1

100 Translational Medicine associated with PIH1D1

0 Patents (Medical) associated with PIH1D1

Literatures (Medical) associated with PIH1D1

01 Apr 2025·Structure

The structure of the R2T complex reveals a different architecture from the related HSP90 cochaperone R2TP

Article

Author: Boskovic, Jasminka ; Úrbez, Cristina ; López-Perrote, Andrés ; Alabadí, David ; Llorca, Oscar ; Fonseca, Sandra ; Rubio, Vicente ; Palacios-Abella, Alberto

The R2TP complex is a specialized HSP90 cochaperone essential for the maturation of macromolecular complexes such as RNAPII and TORC1. R2TP is formed by a hetero-hexameric ring of AAA-ATPases RuvBL1 and RuvBL2, which interact with RPAP3 and PIH1D1. Several R2TP-like complexes have been described, but these are less well characterized. Here, we identified, characterized and determined the cryo-electron microscopy (cryo-EM) structure of R2T from Arabidopsis thaliana, which lacks PIH1D1 and is probably the only form of the complex in seed plants. In contrast to R2TP, R2T is organized as two rings of AtRuvBL1-AtRuvBL2a interacting back-to-back, with one AtRPAP3 anchored per ring. AtRPAP3 has no effect on the ATPase activity of AtRuvBL1-AtRuvBL2a and binds with a different stoichiometry than in human R2TP. We show that the interaction of AtRPAP3 with AtRuvBL2a and AtHSP90 occurs via a conserved mechanism. However, the distinct architectures of R2T and R2TP suggest differences in their functions and mechanisms.

01 Dec 2024·Journal of Molecular Biology

The HSP90/R2TP Quaternary Chaperone Scaffolds Assembly of the TSC Complex

Article

Author: Schaeffer, Christine ; Chagot, Marie-Eve ; M. F. Sousa, Pedro ; Bandeiras, Tiago M. ; Paiva, Ana C F ; Schneider, Justine ; Sousa, Pedro M F ; Busse, Philipp ; Robert, Marie-Cécile ; Paiva, Ana C.F. ; Verheggen, Céline ; Charpentier, Bruno ; Cianferani, Sarah ; Abéza, Claire ; Manival, Xavier ; Bandeiras, Tiago M ; Vandermoere, Franck ; Bertrand, Edouard

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.

01 Feb 2024·Cell Reports

DPCD is a regulator of R2TP in ciliogenesis initiation through Akt signaling

Article

Author: Seraphim, Thiago V ; Babu, Mohan ; Laurent, Estelle ; Mollica, Antonio ; Mennella, Vito ; Houry, Walid A ; Wu, Ruikai ; Wan, Yimei ; Raught, Brian ; Coyaud, Etienne ; Bin Munim, Muhammad ; Mao, Yu-Qian

R2TP is a chaperone complex consisting of the AAA+ ATPases RUVBL1 and RUVBL2, as well as RPAP3 and PIH1D1 proteins. R2TP is responsible for the assembly of macromolecular complexes mainly acting through different adaptors. Using proximity-labeling mass spectrometry, we identified deleted in primary ciliary dyskinesia (DPCD) as an adaptor of R2TP. Here, we demonstrate that R2TP-DPCD influences ciliogenesis initiation through a unique mechanism by interaction with Akt kinase to regulate its phosphorylation levels rather than its stability. We further show that DPCD is a heart-shaped monomeric protein with two domains. A highly conserved region in the cysteine- and histidine-rich domains-containing proteins and SGT1 (CS) domain of DPCD interacts with the RUVBL2 DII domain with high affinity to form a stable R2TP-DPCD complex both in cellulo and in vitro. Considering that DPCD is one among several CS-domain-containing proteins found to associate with RUVBL1/2, we propose that RUVBL1/2 are CS-domain-binding proteins that regulate complex assembly and downstream signaling.

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PIH1D1

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