Structure and Function of RhoBTB1 Required for Substrate Specificity and Cullin-3 Ubiquitination.

ABSTRACT: We identified Rho-related BTB domain containing 1 (RhoBTB1) as a key regulator of phosphodiesterase 5 (PDE5) activity, and through PDE5, a regulator of vascular tone. We identified the binding interface for PDE5 on RhoBTB1 by truncating full-length RhoBTB1 into its component domains. Co-immunoprecipitation analyses revealed that the C-terminal half of RhoBTB1 containing its two BTB domains and the C-terminal domain (B1B2C) is the minimal region required for PDE5 recruitment and subsequent proteasomal degradation via Cullin-3 (CUL3). The C-terminal domain was essential in recruiting PDE5 as constructs lacking this region could not participate in PDE5 binding or proteasomal degradation. We also identified Pro³⁵³ and Ser³⁶³ as key amino acid residues in the B1B2C region

SUBMITTER: Kumar G 

PROVIDER: S-EPMC10413933 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature