Tap42 and Tip41, two PP2A-interacting proteins, act in concert to regulate a subset of rapamycin-induced genes.
Katrin Düvel, James Broach
Dept. of Molecular Biology, Princeton University, Washington Road, Princeton, NJ, 08544, USA
The TOR signaling pathway enables yeast cells to respond to nutrients and adjust cell growth accordingly. The central components of the pathway are the Tor1 and Tor2 protein kinases, which can be inhibited by the drug rapamycin. The TOR pathway affects numerous cellular processes, several of them through the activity of protein phosphatase 2A (PP2A) and the related phosphatase Sit4. The catalytic subunits of these phosphatases interact with the essential protein Tap42. We have shown that transcriptional activation upon rapamycin addition of a large number of genes requires Tap42, Sit4 and the PP2A catalytic subunits, suggesting that Tap42 functions as a coactivator of the PP2A phosphatases in induction of these target genes. Tip41 is a newly identified member of the TOR pathway, which interacts with Tap42 as well as with the PP2A catalytic subunits. Deletion of TIP41 in wild-type strains causes no obvious growth defect at 30°C but elicits a synthetic slow growth phenotype with tap42 mutations. cDNA microarray experiments revealed that loss of TIP41 resulted in mild induction of respiratory genes and, like mutation of TAP42, impaired rapamycin-induction of nitrogen regulated genes. A tip41 tap42ts mutant strain further abolished the response of nitrogen-regulated genes. This suggests that Tip41 and Tap42 play similar roles in activating nitrogen-regulated genes upon rapamycin addition.
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