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Proteomic Alterations in Oncogene-In...

Durbin, Kenneth R.

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Proteomic Alterations in Oncogene-Induced Senescence.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Proteomic Alterations in Oncogene-Induced Senescence./
作者:	Durbin, Kenneth R.
面頁冊數:	252 p.
附註:	Source: Dissertation Abstracts International, Volume: 76-05(E), Section: B.
Contained By:	Dissertation Abstracts International76-05B(E).
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3669215
ISBN:	9781321446722

Proteomic Alterations in Oncogene-Induced Senescence.
Durbin, Kenneth R.

Proteomic Alterations in Oncogene-Induced Senescence. - 252 p.

Source: Dissertation Abstracts International, Volume: 76-05(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2014.

This item is not available from ProQuest Dissertations & Theses.

The study of proteins, proteomics, is necessary to understand the molecular mechanisms involved in disease. Whereas typical proteomic analyses by mass spectrometry involve digestion before analysis, the `top down' approach analyzes intact proteins directly, preserving important transcriptional and post-translational processing information. Recent breakthroughs, particularly in protein separation technology and instrumentation, have enabled top down proteomics to achieve thousands of protein identifications. Here, additional improvements have been realized through alterations to data acquisition logic wrapped in a newly created software environment called Autopilot. Data directly from the instrument is interpreted in real-time and acquisition strategies are tailored towards individual proteins and overall project strategy. Development and use of Autopilot improved the number of proteins identified per unit time, the extent of protein characterization, and the ability to quantify relative expression levels for protein forms <30 kDa in size.

ISBN: 9781321446722Subjects--Topical Terms:

3172791
Cellular biology.

Proteomic Alterations in Oncogene-Induced Senescence.
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245 1 0 $a Proteomic Alterations in Oncogene-Induced Senescence.
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500 $a Source: Dissertation Abstracts International, Volume: 76-05(E), Section: B.
500 $a Includes supplementary digital materials.
500 $a Adviser: Neil L. Kelleher.
502 $a Thesis (Ph.D.)--Northwestern University, 2014.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a The study of proteins, proteomics, is necessary to understand the molecular mechanisms involved in disease. Whereas typical proteomic analyses by mass spectrometry involve digestion before analysis, the `top down' approach analyzes intact proteins directly, preserving important transcriptional and post-translational processing information. Recent breakthroughs, particularly in protein separation technology and instrumentation, have enabled top down proteomics to achieve thousands of protein identifications. Here, additional improvements have been realized through alterations to data acquisition logic wrapped in a newly created software environment called Autopilot. Data directly from the instrument is interpreted in real-time and acquisition strategies are tailored towards individual proteins and overall project strategy. Development and use of Autopilot improved the number of proteins identified per unit time, the extent of protein characterization, and the ability to quantify relative expression levels for protein forms <30 kDa in size.
520 $a Autopilot was employed in both targeted and untargeted modes to study protein-level changes in human fibroblasts undergoing oncogene-induced senescence. On par with the largest top down proteomics study achieved to date, nearly 1500 protein identifications were achieved in only 23% of the acquisition time previously required. Additionally, Autopilot facilitated an expansive quantitative study of intact proteins, with 2387 proteoforms reported on nuclear, cytoplasmic, and mitochondrial cellular compartments. From the quantitative data, oxidative phosphorylation proteins were shown to be upregulated by greater than two-fold in senescence. These findings were corroborated and further supplemented by a companion `bottom-up' proteomics study. Contrary to other metabolic enzymes, quantitated TCA cycle enzymes were demonstrably downregulated in senescence. An untargeted study of proteome-wide acetylation levels revealed major changes in acetylation levels to several enzymes, particularly Lys residues 80 and 384 on the mitochondrial enzyme, IDH2. In senescence, IDH2 activity was increased by 15%, despite four-fold lower IDH2 levels. The enhanced activity of this key TCA cycle enzyme is substantiated by confocal microscopy and flow cytometry data revealing heightened mitochondrial potential. Together, the results indicate the post-translational modification of mitochondrial enzymes leads to an overall increase in aerobic respiration. Additionally, these advances to top down proteomics demonstrate the technology is now capable of significant biological discovery and hypothesis-driven investigation.
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650 4 $a Analytical chemistry. $3 3168300
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793 $a English
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