Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2014-04-12
    Description: Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Anna Y -- St Onge, Robert P -- Proctor, Michael J -- Wallace, Iain M -- Nile, Aaron H -- Spagnuolo, Paul A -- Jitkova, Yulia -- Gronda, Marcela -- Wu, Yan -- Kim, Moshe K -- Cheung-Ong, Kahlin -- Torres, Nikko P -- Spear, Eric D -- Han, Mitchell K L -- Schlecht, Ulrich -- Suresh, Sundari -- Duby, Geoffrey -- Heisler, Lawrence E -- Surendra, Anuradha -- Fung, Eula -- Urbanus, Malene L -- Gebbia, Marinella -- Lissina, Elena -- Miranda, Molly -- Chiang, Jennifer H -- Aparicio, Ana Maria -- Zeghouf, Mahel -- Davis, Ronald W -- Cherfils, Jacqueline -- Boutry, Marc -- Kaiser, Chris A -- Cummins, Carolyn L -- Trimble, William S -- Brown, Grant W -- Schimmer, Aaron D -- Bankaitis, Vytas A -- Nislow, Corey -- Bader, Gary D -- Giaever, Guri -- GM103504/GM/NIGMS NIH HHS/ -- GM44530/GM/NIGMS NIH HHS/ -- MOP-700724/Canadian Institutes of Health Research/Canada -- MOP-79368/Canadian Institutes of Health Research/Canada -- MOP-81340/Canadian Institutes of Health Research/Canada -- P01 HG000205/HG/NHGRI NIH HHS/ -- P41 GM103504/GM/NIGMS NIH HHS/ -- R01 003317-07/PHS HHS/ -- R01 CA157456/CA/NCI NIH HHS/ -- R01 GM044530/GM/NIGMS NIH HHS/ -- R01 HG003317/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):208-11. doi: 10.1126/science.1250217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723613" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cells/*drug effects ; Drug Evaluation, Preclinical/*methods ; Drug Resistance/*genetics ; *Gene Regulatory Networks ; Genome-Wide Association Study/*methods ; Haploinsufficiency ; Humans ; Pharmacogenetics ; Saccharomyces cerevisiae/drug effects/genetics ; Small Molecule Libraries/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2013-06-01
    Description: The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) to promote mTORC1 translocation to the lysosomal surface, its site of activation. Although progress has been made in identifying positive regulators of the Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a complex that interacts with the Rags and is composed of two subcomplexes we call GATOR1 and -2. Inhibition of GATOR1 subunits (DEPDC5, Nprl2, and Nprl3) makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling, and epistasis analysis shows that GATOR2 negatively regulates DEPDC5. GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer. In cancer cells with inactivating mutations in GATOR1, mTORC1 is hyperactive and insensitive to amino acid starvation, and such cells are hypersensitive to rapamycin, an mTORC1 inhibitor. Thus, we identify a key negative regulator of the Rag GTPases and reveal that, like other mTORC1 regulators, Rag function can be deregulated in cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728654/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728654/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bar-Peled, Liron -- Chantranupong, Lynne -- Cherniack, Andrew D -- Chen, Walter W -- Ottina, Kathleen A -- Grabiner, Brian C -- Spear, Eric D -- Carter, Scott L -- Meyerson, Matthew -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- CA103866/CA/NCI NIH HHS/ -- F31 CA180271/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R01 CA129105/CA/NCI NIH HHS/ -- U24CA143867/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1100-6. doi: 10.1126/science.1232044.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723238" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*metabolism ; Carrier Proteins/antagonists & inhibitors/genetics/*metabolism ; Cell Line, Tumor ; GTPase-Activating Proteins ; HEK293 Cells ; Humans ; Lysosomes/*enzymology ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes ; Mutation ; Neoplasms/*enzymology/genetics ; Nuclear Proteins/antagonists & inhibitors/genetics/metabolism ; Proteins/*metabolism ; RNA, Small Interfering/genetics ; TOR Serine-Threonine Kinases ; Tumor Suppressor Proteins/antagonists & inhibitors/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...