Type
Text
Type
Thesis
Advisor
Zachar, Zuzana | Stuart, Shawn
Date
2014-12-01
Keywords
Biochemistry | BCKDC, CPI-613, H460
Department
Department of Biochemistry and Cell Biology.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76908
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
The production of lipids and proteins for growth, as well as nucleotides for the replication of the genome, are key requirements that loom as importantly as the need for the production of energy in the transformed metabolic state of cancer cells. The remodeling of the TCA cycle (extensive anaplerosis and cataplerosis) reflects this need for biosynthetic macromolecules. CPI-613, a non-redox active lipoic acid analog that has been shown to selectively increase phosphorylation of the pyruvate dehydrogenase (PDH) E1 α subunit, thereby inactivating the entire complex, was investigated for its role in causing phosphorylation of the branched-chain amino acid dehydrogenase complex (BCKDC) E1 α subunit in H460 lung cancer cells. CPI-613 was shown to cause hyper-phosphorylation of the peptide via western analysis, which triggered further investigation of the role of the drug in causing similar effects in several other epithelial cancer cell lines, as well as one glioblastoma line. At the current time, BCKDC appears to be a third such lipoate-containing mitochondrial enzyme target of CPI-613. | 36 pages
Recommended Citation
Dahan, Michael Simon, "CPI-613, a non-redox active lipoic acid analog, causes hyper-phosphorylation of BCKDC E1α in H460 lung cancer cells in vitro" (2014). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2782.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2782