Article ; Online: mTORC1 directly phosphorylates and regulates human MAF1.
Molecular and cellular biology
2010 Volume 30, Issue 15, Page(s) 3749–3757
Abstract: mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other ... ...
| Abstract | mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1. |
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| MeSH term(s) | Humans ; Phosphorylation ; RNA Polymerase III/antagonists & inhibitors ; RNA Polymerase III/genetics ; RNA Polymerase III/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Sirolimus/metabolism ; Sirolimus/pharmacology ; Transfection | |||||
| Chemical Substances | RNA Polymerase III (EC 2.7.7.6) ; Sirolimus (W36ZG6FT64) | |||||
| Language | English | |||||
| Publishing date | 2010-06-01 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 779397-2 | |||||
| ISSN | 1098-5549 ; 0270-7306 | |||||
| ISSN (online) | 1098-5549 | |||||
| ISSN | 0270-7306 | |||||
| DOI | 10.1128/MCB.00319-10 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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