Histone-H4 Probe for Deubiquitinase Identification
| Author(s) | Lazarus, Cole | |
| Date Accessioned | 2022-06-16T17:34:07Z | |
| Date Available | 2022-06-16T17:34:07Z | |
| Publication Date | 2021-05 | |
| Abstract | Ubiquitination is a critically important protein post-translational modification. The addition of ubiquitin to substrate protein residues can lead to a wide variety of cellular outcomes. Therefore, this reversible addition is regulated by deubiquitinases (DUBs), proteolytic enzymes that remove ubiquitin protein from the large variety of substrates. Identifying the DUBs responsible for regulating important ubiquitination events in the cell will lead to a better understanding of those processes and may offer novel targets for drug development. Histones are a crucial class of proteins responsible for genome condensation in all eukaryotic cells. They are subject to numerous different post-translational modifications, including ubiquitination. These modifications can have large impacts on gene expression, by changing the chromatin structure. Among the histone proteins,Histone-H4 is one of particular interest to our group, given its role in DNA repair following ubiquitination. Specifically, while ubiquitination of lysine 91 of Histone-H4 has been directly linked to the DNA damage response, little is known about the reverse reaction catalyzed by unknown DUBs. Therefore, my project seeks to identify the DUBs that recognize mono-ubiquitinated histone-H4, by constructing a cell-permeable, activity-based probe. This probe will be assembled with ubiquitin and histone-H4 mutants, modified and synthesized together to enable several functionalities, including recognition of the probe by target DUBs by mimicking the native substrate; delivery of probe into living cells; capture of DUBs via a built in Michael acceptor in the non-cleavable linker; and enrichment of the probe following treatment via a co-transcribed HA tag. | en_US |
| Advisor | Zhihao Zhuang | |
| Program | Biochemistry | |
| URL | https://udspace.udel.edu/handle/19716/31002 | |
| Publisher | University of Delaware | en_US |
| Keywords | Deubiquitinases | en_US |
| Keywords | Histones | en_US |
| Keywords | Ubiquitination | en_US |
| Title | Histone-H4 Probe for Deubiquitinase Identification | en_US |
| Type | Thesis | en_US |