東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Identification and exploration of ap...

Seaman, Julia Elizabeth.

Linked to FindBook

Google Book

Amazon

博客來

Identification and exploration of apoptotic and caspase proteolytic substrates.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Identification and exploration of apoptotic and caspase proteolytic substrates./
Author:	Seaman, Julia Elizabeth.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	216 p.
Notes:	Source: Dissertation Abstracts International, Volume: 77-11(E), Section: B.
Contained By:	Dissertation Abstracts International77-11B(E).
Subject:	Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10133461
ISBN:	9781339920412

Identification and exploration of apoptotic and caspase proteolytic substrates.
Seaman, Julia Elizabeth.

Identification and exploration of apoptotic and caspase proteolytic substrates. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 216 p.

Source: Dissertation Abstracts International, Volume: 77-11(E), Section: B.

Thesis (Ph.D.)--University of California, San Francisco, 2016.

Apoptosis, a type of programmed cell death, is a universal and essential cellular function. There are numerous homeostatic biological roles of apoptosis and many diseases have or cause mys- or dis- regulated apoptosis, most notably cancer's escape from apoptotic signals. Apoptosis has many distinctive characteristics including membrane blebbing, chromatin condensation, and most importantly for these studies, the activation of a class of protease proteins called caspases. Caspases are cysteine aspartic proteases with a unique preference to cleave hundred of substrates after acidic residues, especially aspartate. These cleavage events can activate, modify, or inhibit the substrate's function, which leads to the dismantling of the cell during apoptosis. This process is well conserved throughout metazoan evolution, with parallel pathways in coral, fish, flies, worms and mice.

ISBN: 9781339920412Subjects--Topical Terms:

518028
Biochemistry.

Identification and exploration of apoptotic and caspase proteolytic substrates.
LDR:04827nmm a2200361 4500 001 2117266
005 20170515104722.5
008 180830s2016 ||||||||||||||||| ||eng d
020 $a 9781339920412
035 $a (MiAaPQ)AAI10133461
035 $a AAI10133461
040 $a MiAaPQ $c MiAaPQ
100 1 $a Seaman, Julia Elizabeth. $3 3279036
245 1 0 $a Identification and exploration of apoptotic and caspase proteolytic substrates.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 216 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-11(E), Section: B.
500 $a Adviser: James Wells.
502 $a Thesis (Ph.D.)--University of California, San Francisco, 2016.
520 $a Apoptosis, a type of programmed cell death, is a universal and essential cellular function. There are numerous homeostatic biological roles of apoptosis and many diseases have or cause mys- or dis- regulated apoptosis, most notably cancer's escape from apoptotic signals. Apoptosis has many distinctive characteristics including membrane blebbing, chromatin condensation, and most importantly for these studies, the activation of a class of protease proteins called caspases. Caspases are cysteine aspartic proteases with a unique preference to cleave hundred of substrates after acidic residues, especially aspartate. These cleavage events can activate, modify, or inhibit the substrate's function, which leads to the dismantling of the cell during apoptosis. This process is well conserved throughout metazoan evolution, with parallel pathways in coral, fish, flies, worms and mice.
520 $a To study apoptotic protease activity, the Wells Lab has developed a proteomic-based technique. This technique is an unbiased positive enrichment labeling mass spectrometry protocol. While the protocol was developed for studying caspase substrates during apoptosis in human cell culture, it is very versatile, allowing for use in almost any protein sample like perturbed cellular lysates, different species and primary samples. Chapter 1 covers the protocol specifics and uses, summarizing a decade's worth of optimization and application.
520 $a The DegraBase is the compilation of 44 different experiments using the N-terminal labeling method to examine apoptotic proteolytic activity described in Chapter 2. While much of the experimentation work was completed before I started the project, I completed compilation and standardization of raw data, and worked with Emily Crawford on the analysis. This global analysis reveals there is a large increase in proteolytic activity after apoptotic induction, and caspases account for 25% of the newly created fragments. Within caspase substrates, there is no single biological process or sub-cellular location that is targeted, as caspases appear to cleave substrates throughout all the different pathways of the cell. Additionally, this database is also a good resource for endogenous proteolysis, including free methionines, and signal and transis peptide processing.
520 $a Analysis of the DegraBase also reveals evolutionary and biological discoveries. As the apoptotic pathway to activate caspases is highly conserved throughout metazoans, we wanted to investigate the conservation of caspase substrates. In Chapter 3, the comparison of caspase substrates in worm, fly, mouse and human reveals a hierarchal structure. My contribution includes the murine dataset and comparison analysis in collaboration with Emily Crawford. We found caspase cleavage is highly conserved at the pathway level, while individual targets and sites are not as well conserved the more distant the animals.
520 $a The unbiased and large size of the DegraBase also reveals broader caspase activity than previously described. Caspases had been assumed to have absolute specificity for aspartate and no activity for glutamate. However, with the large dataset, in Chapter 4, I reveal significant activity after glutamate and even potential activity after phosphoserine. This activity is verified through biochemical assays and x-ray crystallography, and expands the number of apoptotic caspase substrates by 15%.
520 $a As many chemotherapeutics induce apoptosis, apoptotic, especially caspase, proteolytic substrates may be good biomarkers of treatment efficacy. The development of mouse models and a positive control are discussed in Chapter 5. These models utilize the DegraBase and labeling technology to identify peptides enriched in the blood and tumor specific to treatment responding mice as potential biomarkers.
590 $a School code: 0034.
650 4 $a Biochemistry. $3 518028
650 4 $a Pharmacology. $3 634543
650 4 $a Oncology. $3 751006
690 $a 0487
690 $a 0419
690 $a 0992
710 2 $a University of California, San Francisco. $b Pharmaceutical Sciences and Pharmacogenomics. $3 1023490
773 0 $t Dissertation Abstracts International $g 77-11B(E).
790 $a 0034
791 $a Ph.D.
792 $a 2016
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10133461