Ping Dou Abstract As the occurrence of breast cancer increases around the world, the need for new therapeutic medicine becomes more vital to sustain the population.
Thesis Abstract Regulated proteolysis plays a major role in diverse cellular processes, including cell-cycle progression, endocytosis, apoptosis, transcription, and signal transduction.
Proteins destined for proteolysis undergo two key steps in the ubiquitin-proteasome pathway.
First, a complex enzymatic cascade controls conjugation of a multiubiquitin chain onto a protein. Once ubiquitinated, protein substrates must be recognized and targeted to the proteasome complex, where they are unfolded and degraded.
Receptor proteins, such as Rad23, recognize ubiquitinated proteins and deliver them to the proteasome.
rutadeltambor.comct Ubiquitin proteasome pathway is an important cellular pathway that affects the fate of almost all intracellular proteins. Misregulation of this pathway has been found to be associated with a broad range of human diseases, such as cancer, neurodegenerative diseases, as well as. Get this from a library! Binding studies of human ubiquitin conjugating enzyme 7 and the experimental demonstration of residual dipolar coupling methodology by nuclear magnetic resonance spectroscopy.. [Briggman, Kathryn B.] -- Binding studies of human ubiquitin conjugating enzyme 7 and the experimental demonstration of residual dipolar coupling methodology by nuclear magnetic resonance. In ubiquitin (Ub) system, E3 ligases have a central role in mediating substrate ubiquitination and triggering substrate degradation or other signalling transductions. RING E3s are the largest family of E3s and they promote direct Ub transfer from E2’s active site to substrate. Some RING E3s require dimerization for their activity, but structural evidence on the importance of dimerization and.
While the list of enzymes involved in ubiquitination is steadily growing, the first enzymatic reaction required for all ubiquitin-dependent processes is catalyzed by one protein, the ubiquitin-activating enzyme, E1.
We report the isolation of uba, a temperature-sensitive allele UBA1 that exhibits dramatic inhibition of the ubiquitin-proteasome pathway. Shifting mutant cells to the restrictive temperature results in the depletion of cellular ubiquitin conjugates within minutes, accompanied by stabilization of multiple protein substrates.
We have employed the tight phenotype of this mutant to investigate the role ubiquitin conjugates play the recognition and delivery of substrates to the proteasome.
It is possible to purify intact and active proteasomes complexes from uba cells. In the absence of ubiquitin activation, these proteasome complexes are depleted of ubiquitin conjugates and the ubiquitin-binding receptor proteins Rad23 and Dsk2.
Binding of Rad23 to these proteasomes in vitro is enhanced by addition of either free or substrate-linked ubiquitin chains. Moreover, association of Rad23 with proteasomes in mutant and wild-type cells is improved upon stabilizing ubiquitin conjugates with proteasome inhibitor.
We propose that recognition of polyubiquitin chains by Rad23 promotes its shuttling to the proteasome in vivo.
As an additional example of the value of this novel genetic mutant in the study of the ubiquitin-proteasome system, we present preliminary results from a quantitative mass spectrometric analysis of the proteins associated with proteasome complexes isolated from uba cells.
In summary, we have created a genetic method of rapidly inhibiting the ubiquitin-proteasome system. This will enable future exploration of the ubiquitin-proteasome system and potentially many other ubiquitin-dependent cellular processes.THE ROLE OF THE UBIQUITIN-PROTEASOME SYSTEM IN NEURODEGENERATIVE DISORDERS Lisette Gerridina Gezina Catharina Verhoef to ubiquitin (Ub).
The ubiquitin-proteasome system (UPS) is the main diseases these proteins accumulate with disastrous consequences for neurons, eventually leading to cell death.
In this thesis, the role of the UPS in. Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8.
The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. The inability of some ubiquitin-like proteins (Ubls) to substitute for ubiquitin indicates that a specific region on the ubiquitin surface is required for hDot1L stimulation, rather than the effect being simply due to steric bulk (23, 24).
My thesis work has mainly focused on the ubiquitin C-terminal hydrolase (UCH) family of DUBs. The biological role and substrates for many of these enzymes has still not been elucidated.
I have worked to characterize these enzymes through structural and biochemical methods to advance our basic understanding of these proteins. Abstract. Monoubiquitylation is a regulatory signal, like phosphorylation, that can alter the activity, location or structure of a protein.
Monoubiquitin signals are likely to be recognized by ubiquitin‐binding proteins that transmit the regulatory information conferred by monoubiquitylation.
Molecular Dynamics simulations on a 17 residues peptide of the N-term of ubiquitin, using two forcefields (AMBER99SB and AMBER99SB-ILDN) in non- and protonated form of the peptide.