Publications by authors named "L G Randles"
The present study sought to manipulate workload individually for participants to evaluate whether individual manipulations of workload produces similar subjective ratings and performance changes across participants. Participants included eight Army-rated rotary-wing aviators who presented to the laboratory for two separate visits. During the first visit, individual responses to workload were determined, and during the second visit, individually manipulated high workload flights were completed.
View Article and Find Full Text PDFArticle Synopsis
- The proteasome-ubiquitin receptor hRpn13/Adrm1 activates the deubiquitinating enzyme Uch37, with bis-benzylidine piperidone RA190 inhibiting cancer growth in mice by targeting this interaction.
- Structural analysis shows hRpn13 and hRpn2 interact closely, with an extension of hRpn2 blocking RA190's binding site on hRpn13.
- RA190 does not impact hRpn13's connection with Uch37 but instead directly inactivates Uch37, leading to a buildup of substrates at proteasomes in hRpn13-deficient cells.
Article Synopsis
- Three receptors in the proteasome (Rpn1/S2/PSMD2, Rpn10/S5a, Rpn13/Adrm1) aid in substrate binding by interacting with ubiquitin chains and shuttle factors that transport substrates to proteasomes.
- Researchers solved the structures of Rpn13 with PLIC2 and Rpn1 with Rad23, revealing that specific amino acid changes in Rad23 and Dsk2 optimize the affinity for Rpn1 and Rpn13.
- A mutation in PLIC2 enhances binding to Rpn13 while blocking its interaction with certain ubiquitin chains, demonstrating that shuttle factors use tailored surfaces to effectively deliver substrates to proteasomes.
Recently, we reported that bisbenzylidine piperidone RA190 adducts to Cys-88 of the proteasome ubiquitin receptor hRpn13, triggering accumulation of ubiquitinated proteins and endoplasmic reticulum stress-related apoptosis in various cancer cell lines. hRpn13 contains an N-terminal pleckstrin-like receptor for ubiquitin domain that binds ubiquitin and docks it into the proteasome as well as a C-terminal deubiquitinase adaptor (DEUBAD) domain that binds the deubiquitinating enzyme Uch37. Here we report that hRpn13 and Uch37 are required for proper cell cycle progression and that their protein knockdown leads to stalling at G0/G1 Moreover, serum-starved cells display reduced hRpn13 and Uch37 protein levels with hallmarks of G0/G1 stalling and recovery to their steady-state protein levels following release from nutrient deprivation.
View Article and Find Full Text PDFMultiple genes in Mycobacterium tuberculosis (Mtb) are regulated by copper including socAB (small orf induced by copper A and B), which is induced by copper and repressed by RicR (regulated in copper repressor). socA and socB encode hypothetical proteins of 61 and 54 amino acids, respectively. Here, we use biophysical and computational methods to evaluate the SocB structure.
View Article and Find Full Text PDF