PMID- 20145209
OWN - NLM
STAT- MEDLINE
DCOM- 20100427
LR  - 20230815
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 3
IP  - 108
DP  - 2010 Feb 9
TI  - ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling 
      pathway.
PG  - ra9
LID - 10.1126/scisignal.2000590 [doi]
AB  - Mammalian target of rapamycin (mTOR) regulates various cellular functions, 
      including tumorigenesis, and is inhibited by the tuberous sclerosis 1 (TSC1)-TSC2 
      complex. Here, we demonstrate that arrest-defective protein 1 (ARD1) physically 
      interacts with, acetylates, and stabilizes TSC2, thereby repressing mTOR 
      activity. The inhibition of mTOR by ARD1 inhibits cell proliferation and 
      increases autophagy, thereby inhibiting tumorigenicity. Correlation between ARD1 
      and TSC2 abundance was apparent in multiple tumor types. Moreover, evaluation of 
      loss of heterozygosity at Xq28 revealed allelic loss in 31% of tested breast 
      cancer cell lines and tumor samples. Together, our findings suggest that ARD1 
      functions as an inhibitor of the mTOR pathway and that dysregulation of the 
      ARD1-TSC2-mTOR axis may contribute to cancer development.
FAU - Kuo, Hsu-Ping
AU  - Kuo HP
AD  - 1Department of Molecular and Cellular Oncology, Unit 108, The University of Texas 
      M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Lee, Dung-Fang
AU  - Lee DF
FAU - Chen, Chun-Te
AU  - Chen CT
FAU - Liu, Mo
AU  - Liu M
FAU - Chou, Chao-Kai
AU  - Chou CK
FAU - Lee, Hong-Jen
AU  - Lee HJ
FAU - Du, Yi
AU  - Du Y
FAU - Xie, Xiaoming
AU  - Xie X
FAU - Wei, Yongkun
AU  - Wei Y
FAU - Xia, Weiya
AU  - Xia W
FAU - Weihua, Zhang
AU  - Weihua Z
FAU - Yang, Jer-Yen
AU  - Yang JY
FAU - Yen, Chia-Jui
AU  - Yen CJ
FAU - Huang, Tzu-Hsuan
AU  - Huang TH
FAU - Tan, Minjia
AU  - Tan M
FAU - Xing, Gang
AU  - Xing G
FAU - Zhao, Yingming
AU  - Zhao Y
FAU - Lin, Chien-Hsing
AU  - Lin CH
FAU - Tsai, Shih-Feng
AU  - Tsai SF
FAU - Fidler, Isaiah J
AU  - Fidler IJ
FAU - Hung, Mien-Chie
AU  - Hung MC
LA  - eng
GR  - P50 CA83639/CA/NCI NIH HHS/United States
GR  - R01 CA109311/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P30 CA016672-34S5/CA/NCI NIH HHS/United States
GR  - CCSG CA16672/CA/NCI NIH HHS/United States
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - P50 CA116199/CA/NCI NIH HHS/United States
GR  - P50 CA083639/CA/NCI NIH HHS/United States
GR  - R01 CA109311-06/CA/NCI NIH HHS/United States
GR  - P50 CA083639-100009/CA/NCI NIH HHS/United States
GR  - P50 CA116199-050005/CA/NCI NIH HHS/United States
GR  - P01 CA099031-01/CA/NCI NIH HHS/United States
GR  - P01 CA099031/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.
DEP - 20100209
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.254 (N-Terminal Acetyltransferase A)
RN  - EC 2.3.1.255 (NAA10 protein, human)
RN  - EC 2.3.1.258 (N-Terminal Acetyltransferase E)
SB  - IM
MH  - Acetyltransferases/*metabolism
MH  - Alleles
MH  - Animals
MH  - Autophagy
MH  - Breast Neoplasms/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Heterozygote
MH  - Humans
MH  - Mice
MH  - N-Terminal Acetyltransferase A
MH  - N-Terminal Acetyltransferase E
MH  - RNA, Small Interfering/metabolism
MH  - *Signal Transduction
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*metabolism
PMC - PMC2874891
MID - NIHMS198006
EDAT- 2010/02/11 06:00
MHDA- 2010/04/28 06:00
PMCR- 2010/05/24
CRDT- 2010/02/11 06:00
PHST- 2010/02/11 06:00 [entrez]
PHST- 2010/02/11 06:00 [pubmed]
PHST- 2010/04/28 06:00 [medline]
PHST- 2010/05/24 00:00 [pmc-release]
AID - 3/108/ra9 [pii]
AID - 10.1126/scisignal.2000590 [doi]
PST - epublish
SO  - Sci Signal. 2010 Feb 9;3(108):ra9. doi: 10.1126/scisignal.2000590.