It is currently unknown if this motif regulates Ch AT function.
The effects of HSP inhibition were greatest for mutant P17A/P19A- and V18M-Ch AT. Lastly, inhibition of the endoplasmic reticulum (ER)- and HSP-associated co-chaperone Cdc48/p97/Valosin-containing protein (VCP) prevented the degradation of ubiquitinated Ch AT.
Together my results identify novel mechanisms for the functional regulation of wild-type and CMS-related mutant Ch AT by multiple molecular chaperones and the ubiquitin-proteasome system that, importantly, may have broader implications for Ch AT function during cellular stress and disease.
We predict that, contrary to the AFM experiments, an additional unfolding peak would occur at the end-to-end $\Delta R \approx 1.5 $nm in the force-extension curve.
Our study reveals the important role of non-native interactions which are responsible for a peak located at $\Delta R \approx 22 $nm.
Defects in ubiquitin-dependent proteolysis have been shown to result in a variety of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders.
The SCF (Skp1-Cullin-F-box-Hrt1) complex is a heteromeric ubiquitin ligase that multiubiquitinates proteins important for signal transduction and cell cycle progression.
A technology was developed known as Protac (Proteolysis Targeting Chimeric Molecule), that acts as a bridge, bringing together the SCF ubiquitin ligase with a protein target, resulting in its ubiquitination and degradation.
The Protac contains a peptide moiety at one end that is recognized by SCF that is chemically linked to the binding partner or ligand of the target protein.
Ph D thesis by Maksim Kouza defended at Institute of Physics Polish Academy of Sciences in 2009 (supervisor Prof.
The enzyme choline acetyltransferase (Ch AT) mediates synthesis of the neurotransmitter acetylcholine required for cholinergic neurotransmission.