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Full-Text Articles in Life Sciences
Uncovering The Ubiquitin Ligase Activity And Substrates Of The Human C-Terminal To Lish (Ctlh) Complex, Matthew E.R. Maitland
Uncovering The Ubiquitin Ligase Activity And Substrates Of The Human C-Terminal To Lish (Ctlh) Complex, Matthew E.R. Maitland
Electronic Thesis and Dissertation Repository
Ubiquitination is the transfer of a ubiquitin molecule to protein substrates by the sequential actions of E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. It is a post-translational modification that controls the fate and function of the substrate protein. Substrate specificity in the ubiquitination reaction is conferred by the E3 ligases. Sequence homology suggests the human C-terminal to LisH (CTLH) complex could be an E3 ligase; however, very little is known about this complex. In this thesis, I characterize the human CTLH complex as a multi-subunit E3 ligase and define its activity, structure, and substrates. I demonstrate that the …
Regulation Of C-Raf Stability By The Ranbpm/Ctlh Complex, Christina J. Mctavish
Regulation Of C-Raf Stability By The Ranbpm/Ctlh Complex, Christina J. Mctavish
Electronic Thesis and Dissertation Repository
RanBPM is an evolutionarily conserved multi-domain protein that has been implicated in the regulation of several cellular process, including protein stability, cell migration, gene transcription, and apoptosis. RanBPM is identified as a key member of the CTLH complex, an orthologous complex to a yeast E3 ubiquitin ligase complex, the exact function of which remains unknown. Previously, our laboratory identified RanBPM as an inhibitor of the ERK1/2 pathway through the modulation of C-RAF protein levels. This study shows that RanBPM-mediated degradation of C-RAF occurs through the proteasome and the entire CRA domain of RanBPM is necessary for direct interaction with C-RAF …
Characterization Of Ranbpm Subcellular Localization And Function In Hdac6 Regulation, Louisa M. Salemi
Characterization Of Ranbpm Subcellular Localization And Function In Hdac6 Regulation, Louisa M. Salemi
Electronic Thesis and Dissertation Repository
RanBPM has been shown to interact with numerous proteins implicating it in a variety of cellular processes including apoptosis, transcription regulation, cell migration, adhesion and morphology and has been shown to have tumour suppressive functions. RanPBM has been hypothesized to be a scaffolding protein and is part of a large protein complex termed the CTLH complex. Although the homologous complex in yeast has been demonstrated to have E3 ubiquitin ligase activity, whether the evolutionarily conserved human complex retains this activity remains to be determined. In this work we aim to characterize the regions of RanBPM that regulate its subcellular localization …