PMID- 17308101
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20211203
IS  - 0008-5472 (Print)
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 4
DP  - 2007 Feb 15
TI  - TSC1 sets the rate of ribosome export and protein synthesis through nucleophosmin 
      translation.
PG  - 1609-17
AB  - Nucleophosmin (B23) is a nucleolar phosphoprotein that has been implicated in 
      numerous cellular processes. In particular, nucleophosmin interacts with 
      nucleolar components of newly synthesized ribosomes to promote ribosome nuclear 
      export. Nucleophosmin is a classic mitogen-induced protein, with changes in its 
      expression correlating with growth factor stimulation. In this study, we examined 
      the underlying mechanism of nucleophosmin induction and showed that 
      hyperproliferative signals emanating from oncogenic H-Ras(V12) cause tremendous 
      increases in nucleophosmin protein expression. Nucleophosmin protein accumulation 
      was dependent on mammalian target of rapamycin (mTOR) activation, as rapamycin 
      completely prevented nucleophosmin induction. Consistent with this finding, 
      genetic ablation of Tsc1, a major upstream inhibitor of mTOR, resulted in 
      nucleophosmin protein induction through increased translation of existing 
      nucleophosmin mRNAs. Increases in nucleophosmin protein accumulation were 
      suppressed by reintroduction of TSC1. Induction of nucleophosmin through Tsc1 
      loss resulted in a greater pool of actively translating ribosomes in the 
      cytoplasm, higher overall rates of protein synthesis, and increased cell 
      proliferation, all of which were dependent on efficient nucleophosmin nuclear 
      export. Nucleophosmin protein accumulation in the absence of Tsc1 promoted the 
      nuclear export of maturing ribosome subunits, providing a mechanistic link 
      between TSC1/mTOR signaling, nucleophosmin-mediated nuclear export of ribosome 
      subunits, protein synthesis levels, and cell growth.
FAU - Pelletier, Corey L
AU  - Pelletier CL
AD  - Division of Molecular Oncology, Department of Internal Medicine, Siteman Cancer 
      Center, Washington University School of Medicine, 660 South Euclid Avenue, St. 
      Louis, MO 63110, USA.
FAU - Maggi, Leonard B Jr
AU  - Maggi LB Jr
FAU - Brady, Suzanne N
AU  - Brady SN
FAU - Scheidenhelm, Danielle K
AU  - Scheidenhelm DK
FAU - Gutmann, David H
AU  - Gutmann DH
FAU - Weber, Jason D
AU  - Weber JD
LA  - eng
GR  - GM 066032/GM/NIGMS NIH HHS/United States
GR  - U01 CA 84314/CA/NCI NIH HHS/United States
GR  - T32 GM007200/GM/NIGMS NIH HHS/United States
GR  - 5T32 GM 07200/GM/NIGMS NIH HHS/United States
GR  - R01 GM066032/GM/NIGMS NIH HHS/United States
GR  - R01 GM066032-05/GM/NIGMS NIH HHS/United States
GR  - U01 CA084314/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.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Chromones)
RN  - 0 (Morpholines)
RN  - 0 (NPM1 protein, human)
RN  - 0 (Npm1 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (TSC1 protein, human)
RN  - 0 (Tsc1 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 117896-08-9 (Nucleophosmin)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Chromones/pharmacology
MH  - Humans
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Nuclear Proteins/biosynthesis/genetics/*metabolism
MH  - Nucleophosmin
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Protein Biosynthesis
MH  - Protein Kinases/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Ribosomes/*metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tumor Suppressor Proteins/deficiency/genetics/*metabolism
MH  - ras Proteins/metabolism
PMC - PMC2859708
MID - NIHMS47495
EDAT- 2007/02/20 09:00
MHDA- 2007/03/16 09:00
PMCR- 2010/04/26
CRDT- 2007/02/20 09:00
PHST- 2007/02/20 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2007/02/20 09:00 [entrez]
PHST- 2010/04/26 00:00 [pmc-release]
AID - 67/4/1609 [pii]
AID - 10.1158/0008-5472.CAN-06-2875 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Feb 15;67(4):1609-17. doi: 10.1158/0008-5472.CAN-06-2875.