Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips

Huang, Jing; Zhu, Heng; Haggarty, Stephen J.; Spring, David R.; Hwang, Heejun; Jin, Fulai; Snyder, M; Schreiber, Stuart L.

doi:10.1073/pnas.0407117101

Cited by 230 publications

(172 citation statements)

References 33 publications

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“…Overexpression of GTR2 or EGO3 increases rapamycin resistance (Dubouloz et al, 2005), and EGO3 is the target of a synthetic molecule (SMIR4) that promotes rapamycin resistance. Furthermore, transcript profiling suggests that ego3 mutants show considerable similarities to rapamycin treated cells (Huang et al, 2004). These observations strongly suggest that EGOC acts upstream of TORC1.…”

Section: Regulation Of Mtorc1 By Nutrient Abundancementioning

confidence: 75%

The TOR signalling network from yeast to man

Virgilio

Loewith

2006

The International Journal of Biochemistry & Cell Biology

208

162

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The target of rapamycin, TOR, is an essential ser/thr protein kinase that functions in two distinct multiprotein complexes, TOR complex 1 and 2. The structure and functions of these complexes have been conserved from yeast to man. TOR complex 1 is inhibited by rapamycin and is thought to couple growth cues to cellular metabolism; TOR complex 2 is not inhibited by rapamycin and appears to regulate spatial aspects of growth such as cell polarity. Work done in a variety of model systems, continues to contribute to our current understanding of this TOR signalling network. Recent studies in flies and mammalian tissue culture cells have elucidated many signalling components upstream of TOR complex 1. These studies also suggest that aberrant mammalian TOR complex 1 signalling contributes to a number of pathologies ranging from metabolic diseases to hyperproliferative disorders and cancers. Consequently the efficacies of rapamycin and related compounds in treating such diseases are being evaluated in clinical trials.

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Section: Regulation Of Mtorc1 By Nutrient Abundancementioning

confidence: 75%

The TOR signalling network from yeast to man

Virgilio

Loewith

2006

The International Journal of Biochemistry & Cell Biology

208

162

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“…The basic premise of high-density arraying has since been expanded to create protein arrays for probing protein-protein or protein-small molecule interactions 18,19 , carbohydrate arrays 20 , tissue arrays 21 and smallmolecule arrays 22 . In a twist of the canonical microarraying technique, the cell microarray, nucleic acids are printed in defined locations on a glass slide and used to transfect cells added on top of the microarray 5 .…”

Section: Overexpression Cell Microarraysmentioning

confidence: 99%

Cell microarrays and RNA interference chip away at gene function

2005

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S25 P E R S P E C T I V EThe recent development of cell microarrays offers the potential to accelerate high-throughput functional genetic studies. The widespread use of RNA interference (RNAi) has prompted several groups to fabricate RNAi cell microarrays that make possible discrete, in-parallel transfection with thousands of RNAi reagents on a microarray slide. Though still a budding technology, RNAi cell microarrays promise to increase the efficiency, economy and ease of genome-wide RNAi screens in metazoan cells.

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“…Protein chips have been used to test for specific protein or nucleic acid binding, and for a variety of biochemical activities, including protein phosphorylation. [77][78][79][80][81][82] The results from these studies have already demonstrated the immense potential of this technology and indicate how it could revolutionize the way we carry out particular types of biochemical analyses.…”

Section: Protein Chips or Proteome Microarraysmentioning

confidence: 95%