Document Detail

Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines.
MedLine Citation:
PMID:  21930909     Owner:  NLM     Status:  MEDLINE    
We previously described four small molecules that reduced the growth of lung adenocarcinoma cell lines with either epidermal growth factor receptor (EGFR) or KRAS mutations in a high-throughout chemical screen. By combining affinity proteomics and gene expression analysis, we now propose superoxide dismutase 1 (SOD1) as the most likely target of one of these small molecules, referred to as lung cancer screen 1 (LCS-1). siRNAs against SOD1 slowed the growth of LCS-1 sensitive cell lines; conversely, expression of a SOD1 cDNA increased proliferation of H358 cells and reduced sensitivity of these cells to LCS-1. In addition, SOD1 enzymatic activity was inhibited in vitro by LCS-1 and two closely related analogs. These results suggest that SOD1 is an LCS-1-binding protein that may act in concert with mutant proteins, such as EGFR and KRAS, to promote cell growth, providing a therapeutic target for compounds like LCS-1.
Romel Somwar; Hediye Erdjument-Bromage; Erik Larsson; David Shum; William W Lockwood; Guangli Yang; Chris Sander; Ouathek Ouerfelli; Paul J Tempst; Hakim Djaballah; Harold E Varmus
Related Documents :
6380839 - Peripolesis followed by cytotoxicity in chronic idiopathic inflammatory bowel disease.
17168519 - Lighting up the nascent cell wall.
2678329 - Effects of subinhibitory dose of amphotericin b on cell wall biosynthesis in candida al...
10845409 - Pharmacological properties of parenteral cephalosporins: rationale for ambulatory use.
6223209 - Chitin synthesis and localization in cell division cycle mutants of saccharomyces cerev...
15587079 - Using wood creep data to discuss the contribution of cell-wall reinforcing material.
17460259 - Localization of zo-1 in the nucleolus of corneal fibroblasts.
15084309 - The werner syndrome protein has separable recombination and survival functions.
8731339 - The effect of light on the biosynthesis of beta-carotene and superoxide dismutase activ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-19
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-28     Completed Date:  2011-11-21     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16375-80     Citation Subset:  IM    
High Throughput Screening Core Facility, and Organic Synthesis Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. or
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adenocarcinoma / enzymology,  pathology*
Cell Division / drug effects*
Cell Line, Tumor
Gene Expression Profiling
Lung Neoplasms / enzymology,  pathology*
RNA, Small Interfering / genetics
Superoxide Dismutase / drug effects,  genetics,  metabolism*
Grant Support
P01 CA129243-03/CA/NCI NIH HHS; P30 CA08748/CA/NCI NIH HHS
Reg. No./Substance:
0/RNA, Small Interfering; EC 1.15.1.-/superoxide dismutase 1; EC Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cr...
Next Document:  Coincident light and clock regulation of pseudoresponse regulator protein 37 (PRR37) controls photop...