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| Status |
Public on Dec 18, 2019 |
| Title |
RUVBL1/RUVBL2 ATPase Activity Drives PAQosome Maturation, DNA Replication and Radioresistance in Lung Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
RUVBL1 and RUVBL2 (collectively RUVBL1/2) are essential AAA+ ATPases that function as co-chaperones and have been implicated in cancer. Here we investigated the molecular and phenotypic role of RUVBL1/2 ATPase activity in non-small cell lung cancer (NSCLC). We find that RUVBL1/2 are overexpressed in NSCLC patient tumors, with high expression prognostic of poor survival. Utilizing a highly specific inhibitor of RUVBL1/2 ATPase activity, we show that RUVBL1/2 ATPase activity is necessary for the maturation of the PAQosome, a large RUVBL1/2-dependent multiprotein complex. We also show that RUVBL1/2 have roles in DNA replication, as inhibition of their ATPase activity impedes RPA loading at replication forks, decreases fork stability, and ultimately results in replication catastrophe and cancer cell death. While in vivo pharmacological inhibition of RUVBL1/2 results in modest antitumor activity, it synergizes with radiation in NSCLC, but not normal cells, an attractive property for future preclinical development.
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| Overall design |
Analyze the transcriptomic response of RUVBL1 knockdown (siBL1) or RUVBL1 inhibition (compB) in two different non-small cell lung cancer cell lines (H2009 and H596)
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| Contributor(s) |
Yenerall P, Das AK, Wang S, Kollipara RK, Li L, Villalobos P, Flaming J, Lin Y, Huffman K, Timmons BC, Gilbreath C, Sonavane R, Kinch LN, Rodriguez-Canales J, Moran C, Behrens C, Hirasawa M, Takata T, Murakami R, Iwanaga K, Chen BP, Grishin NV, Raj GV, Wistuba II, Minna JD, Kittler R |
| Citation(s) |
31883965 |
| Submission date |
Dec 04, 2017 |
| Last update date |
Mar 18, 2020 |
| Contact name |
Ralf Kittler |
| E-mail(s) |
Ralf.Kittler@UTSouthwestern.edu
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| Organization name |
University of Texas Southwestern Medical Center
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| Street address |
5323 Harry Hines Blvd
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| City |
Dallas |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA420950 |
| SRA |
SRP126055 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107637_H2009_H596_compB_compC_fpkm_matrix_whole_genome_fpkm_1.txt.gz |
623.0 Kb |
(ftp)(http) |
TXT |
| GSE107637_H2009_siBL1_fpkm_matrix_whole_genome_fpkm_1.txt.gz |
215.8 Kb |
(ftp)(http) |
TXT |
| GSE107637_H596_siBL1_fpkm_matrix_whole_genome_fpkm_1.txt.gz |
219.2 Kb |
(ftp)(http) |
TXT |
| GSE107637_RAW.tar |
170.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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