Substrate recognition and function of the R2TP complex in response to cellular stress

Area of Science:

• Molecular Biology
• Cellular Biology
• Biochemistry

Background:

• The R2TP complex is an HSP90 co-chaperone essential for cellular processes.
• It comprises four subunits: PIH1D1, RPAP3, RUVBL1, and RUVBL2.
• The complex is crucial for assembling large protein or protein-RNA complexes like RNA polymerase and PIKKs.

Purpose of the Study:

• To provide an overview of the R2TP complex.
• To focus on recently identified structural and mechanistic features of its functions.
• To discuss its role in cellular stress response and potential as an anti-cancer target.

Main Methods:

• Literature review of structural and mechanistic studies.
• Analysis of R2TP complex subunit functions (PIH1D1, RPAP3, RUVBL1, RUVBL2).
• Discussion of R2TP's role in cellular stress response pathways.

Main Results:

• RPAP3 possesses an HSP90 binding domain.
• RUVBLs exhibit ATPase activities critical for R2TP function.
• PIH1D1's PIH-N domain recognizes phosphorylated R2TP substrates.

Conclusions:

• The R2TP complex plays a significant role in cellular homeostasis and stress response.
• Understanding its structure and mechanism offers insights into DNA damage and nutrient deprivation responses.
• The R2TP complex presents a potential therapeutic target for anti-cancer strategies.