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Full-Text Articles in Molecular Biology

The Molecular Basis Of Substrate Recognition By The Family Of Pellino E3 Ubiquitin Ligases, Yu-San Huoh Jan 2013

The Molecular Basis Of Substrate Recognition By The Family Of Pellino E3 Ubiquitin Ligases, Yu-San Huoh

Publicly Accessible Penn Dissertations

The four mammalian Pellinos (Pellinos 1, 2, 3a, and 3b) are E3 ubiquitin ligases that have emerging roles in the regulation of Toll-like receptors, interleukin-1 receptor, T-cell receptor, Nod2, and TNF receptor signaling pathways. While each Pellino has a distinct role in facilitating various cellular processes, the underlying mechanisms by which these highly homologous proteins act selectively in these signaling pathways are not clear. In this dissertation, we elucidate the molecular basis of Pellino substrate specificity in order to gain a better understanding of the roles that individual Pellinos play in orchestrating inflammation and cell death. Pellino substrate recognition is ...


Nucleic Acid Determinants Of Cytosine Deamination By Aid/Apobec Enzymes In Immunity And Epigenetics, Christopher Nabel Jan 2013

Nucleic Acid Determinants Of Cytosine Deamination By Aid/Apobec Enzymes In Immunity And Epigenetics, Christopher Nabel

Publicly Accessible Penn Dissertations

A multitude of functions have evolved around cytosine within DNA, endowing the base with physiological significance beyond simple information storage. This versatility arises from enzymes that chemically modify cytosine to expand the potential of the genome. Cytosine can be methylated, oxidized, and deaminated to modulate transcription and immunologic diversity. At the crossroads of these modifications sit the AID/APOBEC family deaminases, which accomplish diverse functions ranging from antibody diversification and innate immunity to mRNA editing. In addition, novel roles have been proposed in oncogenesis and DNA demethylation. Behind these established and emerging physiologic activities remain important questions about the substrate ...


Molecular Mechanisms Of Alternative Splicing Regulation: An Investigation Of The Spliceosome Repressed By Hnrnp L On Cd45 Exon 4, Ni-Ting Chiou Jan 2013

Molecular Mechanisms Of Alternative Splicing Regulation: An Investigation Of The Spliceosome Repressed By Hnrnp L On Cd45 Exon 4, Ni-Ting Chiou

Publicly Accessible Penn Dissertations

Alternative splicing is a key step in gene regulation and involves the differential selection of splice sites to generate different pre-mRNA transcripts. It has been shown that 90-95% of pre-mRNAs are alternatively spliced in human cells. Pre-mRNA splicing is catalyzed the spliceosome, which consists mainly of the U1, U2, U4, U5 and U6 snRNP, and about a hundred of non-snRNP proteins. Splicing regulators that bind to enhancer or silencer elements on the pre-mRNA can alter assembly of these spliceosome components. Understanding how splicing regulators control spliceosome assembly will bring insights to the prediction of splice site choices. In our lab ...


Control Of The Tumor Suppressor P53 By Regulating Mdm2 Activity And Stability, Ruchira S. Ranaweera Jan 2013

Control Of The Tumor Suppressor P53 By Regulating Mdm2 Activity And Stability, Ruchira S. Ranaweera

Publicly Accessible Penn Dissertations

p53 is a tumor suppressor that is widely mutated or deleted in cancer cells. Mdm2, an E3 ubiquitin ligase, is the master regulator of p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. There are complex regulatory mechanisms balancing the activity and stability of Mdm2 in a cell. Mdm2 has an extremely short half-life in the unstressed cell and its regulation is not well understood. Like most E3 ligases, Mdm2 can autoubiquitinate. Previously, the sole function of autoubiquitination was thought to be to signal Mdm2 degradation. Here I show that ...