자료유형  

 학위논문

Control Number  

0017162037

International Standard Book Number  

9798382768625

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Lowe, Troy Lucas.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, Los Angeles., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

184 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

General Note  

Advisor: Clarke, Steven G.

Dissertation Note  

Thesis (Ph.D.)--University of California, Los Angeles, 2024.

Summary, Etc.  

요약Post translational modifications of proteins alter the biological landscape creating functional diversity. One modification, arginine methylation, was first identified in 1968 from calf thymus hydrolysates producing guanidino-methylated arginine derivatives. However, the enzymes that produce these modifications were poorly characterized until 1996 when the genes of the first protein arginine methyltransferases were cloned from yeast and mammalian cells. At this time, a family of nine mammalian genes has been identified that encode protein arginine methyltransferases (PRMTs). In vitro experiments identified three distinct types. Type I PRMTs catalyze asymmetric dimethylarginine (ADMA) (PRMTs 1-4, 6 and 8), Type II PRMTs catalyze symmetric dimethylarginine (SDMA) (PRMT5 and 9), and the only type III PRMT that catalyzes monomethylarginine (MMA) (PRMT7). The active sites of each of the major enzymes that form ADMA, SDMA and MMA have distinct structural architectures allowing for their specificity.In this dissertation I have focused my work on the major type I enzyme, PRMT1, the major type II enzyme, PRMT5, and the type III enzyme, PRMT7. I showed that each of these human enzymes behave differently under physiological stress conditions associated with temperature, pH, and ionic strength thus potentially leading to alterations in the proteomic arginine methylation landscape. In particular, PRMT7 is maximally active at sub-physiological temperatures and at nonphysiological pH and ionic strength, suggesting regulatory roles. I then characterized the unusual substrate specificity of the PRMT7 enzyme with peptide substrates to demonstrate the exquisite dependence upon variations of the Arg-X-Arg motif.With the identification of a PRMT7 motif in the human Fhod1 and Fhod3 actin binding proteins, I characterized methylation reactions that were dependent upon the phosphorylation state of an adjacent serine residue. These results pointed to the cross-talk that can occur between phosphorylation and methylation reactions. Interestingly, I found little or no effect of methylation on ROCK1 protein kinase activity.PRMT enzymes have been identified to be oncogenic and closely associated with cancer progression. Surprisingly, it was found that methionine-dependent malignant cancer cells had no detectable alteration of protein arginine methylation than methionine-independent less malignant cells, suggesting that the methionine effect maybe be regulated through alternative pathways.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Cellular biology.

Index Term-Uncontrolled  

Arginine methylation

Index Term-Uncontrolled  

Enzymology

Index Term-Uncontrolled  

Post translational modifications

Index Term-Uncontrolled  

PRMT1

Index Term-Uncontrolled  

PRMT7

Index Term-Uncontrolled  

Protein arginine methyltransferases

Added Entry-Corporate Name  

University of California, Los Angeles Chemistry 0153

Host Item Entry  

Dissertations Abstracts International. 85-11B.

Electronic Location and Access  

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Control Number  

joongbu:656791