PMID- 21878679
OWN - NLM
STAT- MEDLINE
DCOM- 20111219
LR  - 20211203
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 4
IP  - 188
DP  - 2011 Aug 30
TI  - AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome 
      biogenesis in cancer.
PG  - ra56
LID - 10.1126/scisignal.2001754 [doi]
AB  - Precise regulation of ribosome biogenesis is fundamental to maintain normal cell 
      growth and proliferation, and accelerated ribosome biogenesis is associated with 
      malignant transformation. Here, we show that the kinase AKT regulates ribosome 
      biogenesis at multiple levels to promote ribosomal RNA (rRNA) synthesis. 
      Transcription elongation by RNA polymerase I, which synthesizes rRNA, required 
      continuous AKT-dependent signaling, an effect independent of AKT's role in 
      activating the translation-promoting complex mTORC1 (mammalian target of 
      rapamycin complex 1). Sustained inhibition of AKT and mTORC1 cooperated to reduce 
      rRNA synthesis and ribosome biogenesis by additionally limiting RNA polymerase I 
      loading and pre-rRNA processing. In the absence of growth factors, constitutively 
      active AKT increased synthesis of rRNA, ribosome biogenesis, and cell growth. 
      Furthermore, AKT cooperated with the transcription factor c-MYC to 
      synergistically activate rRNA synthesis and ribosome biogenesis, defining a 
      network involving AKT, mTORC1, and c-MYC as a master controller of cell growth. 
      Maximal activation of c-MYC-dependent rRNA synthesis in lymphoma cells required 
      AKT activity. Moreover, inhibition of AKT-dependent rRNA transcription was 
      associated with increased lymphoma cell death by apoptosis. These data indicate 
      that decreased ribosome biogenesis is likely to be a fundamental component of the 
      therapeutic response to AKT inhibitors in cancer.
FAU - Chan, Joanna C
AU  - Chan JC
AD  - Division of Research, Peter MacCallum Cancer Centre, St Andrews Place, East 
      Melbourne, Victoria 8006, Australia.
FAU - Hannan, Katherine M
AU  - Hannan KM
FAU - Riddell, Kim
AU  - Riddell K
FAU - Ng, Pui Yee
AU  - Ng PY
FAU - Peck, Abigail
AU  - Peck A
FAU - Lee, Rachel S
AU  - Lee RS
FAU - Hung, Sandy
AU  - Hung S
FAU - Astle, Megan V
AU  - Astle MV
FAU - Bywater, Megan
AU  - Bywater M
FAU - Wall, Meaghan
AU  - Wall M
FAU - Poortinga, Gretchen
AU  - Poortinga G
FAU - Jastrzebski, Katarzyna
AU  - Jastrzebski K
FAU - Sheppard, Karen E
AU  - Sheppard KE
FAU - Hemmings, Brian A
AU  - Hemmings BA
FAU - Hall, Michael N
AU  - Hall MN
FAU - Johnstone, Ricky W
AU  - Johnstone RW
FAU - McArthur, Grant A
AU  - McArthur GA
FAU - Hannan, Ross D
AU  - Hannan RD
FAU - Pearson, Richard B
AU  - Pearson RB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (DNA, Ribosomal)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Ribosomal)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.7.6 (RNA Polymerase I)
SB  - IM
MH  - Cell Division
MH  - DNA, Ribosomal/genetics
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes
MH  - Neoplasms/enzymology/metabolism/*pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Proto-Oncogene Proteins c-myc/*metabolism
MH  - RNA Polymerase I/metabolism
MH  - RNA, Ribosomal/*biosynthesis
MH  - *Ribosomes
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Transcription, Genetic
EDAT- 2011/09/01 06:00
MHDA- 2011/12/20 06:00
CRDT- 2011/09/01 06:00
PHST- 2011/09/01 06:00 [entrez]
PHST- 2011/09/01 06:00 [pubmed]
PHST- 2011/12/20 06:00 [medline]
AID - 4/188/ra56 [pii]
AID - 10.1126/scisignal.2001754 [doi]
PST - ppublish
SO  - Sci Signal. 2011 Aug 30;4(188):ra56. doi: 10.1126/scisignal.2001754.