NDLI: Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism.

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Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism.

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Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	La, Ping Yang, Guang Dennery, Phyllis A.
Description	Author Affiliation: La P ( Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. lap@email.chop.edu)
Abstract	The scaffold protein ISCU facilitates the assembly of iron-sulfur clusters (ISCs), which are essential cofactors for many vital metabolic processes. The mTOR pathways are central to nutrient and energy-sensing networks. Here, we demonstrate that mTORC1 associates with ISCU and phosphorylates ISCU at serine 14. This phosphorylation stabilized ISCU protein. Insufficiency of ISCU triggered by mTORC1 inhibition prevented ISC assembly. Sustained ISCU protein levels enhanced by mTORC1 sensitized TSC2-null cells to iron deprivation due to constitutive ISC biogenesis-triggered iron demand, which outstrips supply. We conclude that the mTORC1 pathway serves to modulate iron metabolism and homeostasis, and we speculate that iron deprivation may be an adjunct in the treatment of cancers characterized by constitutive mTORC1 activation.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	18
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-05-03
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Iron-Sulfur Proteins Metabolism Proteins TOR Serine-Threonine Kinases 3T3-L1 Cells Animals HeLa Cells Homeostasis Physiology Genetics Mice Multiprotein Complexes Phosphorylation Protein Stability Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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