PMID- 22795129
OWN - NLM
STAT- MEDLINE
DCOM- 20130130
LR  - 20230815
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 47
IP  - 4
DP  - 2012 Aug 24
TI  - TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1.
PG  - 535-46
LID - 10.1016/j.molcel.2012.06.009 [doi]
AB  - The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 
      complex, which limits cell growth in response to poor growth conditions. Through 
      its GTPase-activating protein (GAP) activity toward Rheb, this complex inhibits 
      the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a key promoter of 
      cell growth. Here, we identify and biochemically characterize TBC1D7 as a stably 
      associated and ubiquitous third core subunit of the TSC1-TSC2 complex. We 
      demonstrate that the TSC1-TSC2-TBC1D7 (TSC-TBC) complex is the functional complex 
      that senses specific cellular growth conditions and possesses Rheb-GAP activity. 
      Sequencing analyses of samples from TSC patients suggest that TBC1D7 is unlikely 
      to represent TSC3. TBC1D7 knockdown decreases the association of TSC1 and TSC2 
      leading to decreased Rheb-GAP activity, without effects on the localization of 
      TSC2 to the lysosome. Like the other TSC-TBC components, TBC1D7 knockdown results 
      in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell 
      growth under poor growth conditions.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Dibble, Christian C
AU  - Dibble CC
AD  - Department of Genetics and Complex Diseases, Harvard School of Public Health, 
      Boston, MA 02115, USA.
FAU - Elis, Winfried
AU  - Elis W
FAU - Menon, Suchithra
AU  - Menon S
FAU - Qin, Wei
AU  - Qin W
FAU - Klekota, Justin
AU  - Klekota J
FAU - Asara, John M
AU  - Asara JM
FAU - Finan, Peter M
AU  - Finan PM
FAU - Kwiatkowski, David J
AU  - Kwiatkowski DJ
FAU - Murphy, Leon O
AU  - Murphy LO
FAU - Manning, Brendan D
AU  - Manning BD
LA  - eng
GR  - P30-CA006516/CA/NCI NIH HHS/United States
GR  - P01 CA120964/CA/NCI NIH HHS/United States
GR  - R01 CA122617/CA/NCI NIH HHS/United States
GR  - P01-CA120964/CA/NCI NIH HHS/United States
GR  - P30 CA006516/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
DEP - 20120712
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Carrier Proteins)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Neuropeptides)
RN  - 0 (Proteins)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 0 (TBC1D7 protein, human)
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Carrier Proteins/genetics/*metabolism
MH  - GTPase-Activating Proteins/genetics/metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lysosomes/genetics/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Molecular Sequence Data
MH  - Monomeric GTP-Binding Proteins/genetics/metabolism
MH  - Multiprotein Complexes
MH  - Neuropeptides/genetics/metabolism
MH  - Protein Binding
MH  - Proteins/genetics/*metabolism
MH  - Ras Homolog Enriched in Brain Protein
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/genetics/*metabolism
PMC - PMC3693578
MID - NIHMS389079
EDAT- 2012/07/17 06:00
MHDA- 2013/01/31 06:00
PMCR- 2013/08/24
CRDT- 2012/07/17 06:00
PHST- 2012/02/08 00:00 [received]
PHST- 2012/05/03 00:00 [revised]
PHST- 2012/06/05 00:00 [accepted]
PHST- 2012/07/17 06:00 [entrez]
PHST- 2012/07/17 06:00 [pubmed]
PHST- 2013/01/31 06:00 [medline]
PHST- 2013/08/24 00:00 [pmc-release]
AID - S1097-2765(12)00504-7 [pii]
AID - 10.1016/j.molcel.2012.06.009 [doi]
PST - ppublish
SO  - Mol Cell. 2012 Aug 24;47(4):535-46. doi: 10.1016/j.molcel.2012.06.009. Epub 2012 
      Jul 12.