PMID- 26017155
OWN - NLM
STAT- MEDLINE
DCOM- 20160412
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 14
IP  - 13
DP  - 2015
TI  - mTORC1 signaling activates NRF1 to increase cellular proteasome levels.
PG  - 2011-7
LID - 10.1080/15384101.2015.1044188 [doi]
AB  - Defects in the maintenance of protein homeostasis, or proteostasis, has emerged 
      as an underlying feature of a variety of human pathologies, including 
      aging-related diseases. Proteostasis is achieved through the coordinated action 
      of cellular systems overseeing amino acid availability, mRNA translation, protein 
      folding, secretion, and degradation. The regulation of these distinct systems 
      must be integrated at various points to attain a proper balance. In a recent 
      study, we found that the mechanistic target of rapamycin (mTOR) complex 1 
      (mTORC1) pathway, well known to enhance the protein synthesis capacity of cells 
      while concordantly inhibiting autophagy, promotes the production of more 
      proteasomes. Activation of mTORC1 genetically, through loss of the tuberous 
      sclerosis complex (TSC) tumor suppressors, or physiologically, through growth 
      factors or feeding, stimulates a transcriptional program involving the 
      sterol-regulatory element binding protein 1 (SREBP1) and nuclear factor 
      erythroid-derived 2-related factor 1 (NRF1; also known as NFE2L1) transcription 
      factors leading to an increase in cellular proteasome content. As discussed here, 
      our findings suggest that this increase in proteasome levels facilitates both the 
      maintenance of proteostasis and the recovery of amino acids in the face of an 
      increased protein load consequent to mTORC1 activation. We also consider the 
      physiological and pathological implications of this unexpected new downstream 
      branch of mTORC1 signaling.
FAU - Zhang, Yinan
AU  - Zhang Y
AD  - a Department of Genetics and Complex Diseases; Harvard T.H. Chan School of Public 
      Health ; Boston , MA , USA.
FAU - Manning, Brendan D
AU  - Manning BD
LA  - eng
GR  - P01-CA120964/CA/NCI NIH HHS/United States
GR  - R01-CA122617/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20150527
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NRF1 protein, human)
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Cell Membrane/metabolism
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/*metabolism
MH  - Nuclear Respiratory Factor 1/*metabolism
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4613906
OTO - NOTNLM
OT  - NFE2L1
OT  - NRF2
OT  - aging
OT  - cancer
OT  - muscle
OT  - neurodegeneration
OT  - proteasome
OT  - synaptic plasticity
EDAT- 2015/05/29 06:00
MHDA- 2016/04/14 06:00
PMCR- 2016/05/27
CRDT- 2015/05/29 06:00
PHST- 2015/05/29 06:00 [entrez]
PHST- 2015/05/29 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
PHST- 2016/05/27 00:00 [pmc-release]
AID - 1044188 [pii]
AID - 10.1080/15384101.2015.1044188 [doi]
PST - ppublish
SO  - Cell Cycle. 2015;14(13):2011-7. doi: 10.1080/15384101.2015.1044188. Epub 2015 May 
      27.