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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
X-Linked Ubiquitin-Specific Peptidase 11 Increases Tauopathy Vulnerability In Women, Yan Yan
X-Linked Ubiquitin-Specific Peptidase 11 Increases Tauopathy Vulnerability In Women, Yan Yan
USF Tampa Graduate Theses and Dissertations
Women experience significantly higher tau burden and increased risk for Alzheimer’s disease (AD) than men, yet the underlying mechanism for this vulnerability has not been explained. Here, we demonstrate through in vitro and in vivo models, as well as human AD brain tissue, that X-linked ubiquitin specific peptidase 11 (USP11) augments pathological tau aggregation via tau deubiquitination initiated at lysine-281. Removal of ubiquitin provides access for enzymatic tau acetylation at lysines 281 and 274. USP11 escapes complete X-inactivation, and female mice and people both exhibit higher USP11 levels than males. Genetic elimination of usp11 in a tauopathy mouse model preferentially …
Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss
Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss
USF Tampa Graduate Theses and Dissertations
Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction to …
Regulation Of Extracellular Signal-Regulated Kinase By Histone Deacetylase 6, Jheng-Yu Wu
Regulation Of Extracellular Signal-Regulated Kinase By Histone Deacetylase 6, Jheng-Yu Wu
USF Tampa Graduate Theses and Dissertations
Extracellular signal-regulated kinases 1/2 (ERK1/2) are important kinases regulating cell proliferation and cell migration, and have been established as therapeutic targets for cancer treatment. Previously, we found that ERK1 phosphorylates histone deacetylase 6 (HDAC6) to regulate its enzymatic activity. However, whether HDAC6 reciprocally modulates ERK1 activity is unknown. Here, we have discovered that ERK1/2 are acetylated proteins and shown that HDAC6 manipulates ERK1’s kinase activity via deacetylation. We demonstrated that both ERK1 and ERK2 interact with HDAC6 physically. We showed that the acetylation level of GST-ERK1/2 increased in a dose- and time-dependent manner upon treatment with a pan-HDAC inhibitor, Trichostatin …