PMID- 15545626
OWN - NLM
STAT- MEDLINE
DCOM- 20050401
LR  - 20211203
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 18
IP  - 23
DP  - 2004 Dec 1
TI  - The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by 
      down-regulating S6K activity upstream of TSC in Drosophila.
PG  - 2879-92
AB  - Diverse extrinsic and intrinsic cues must be integrated within a developing 
      organism to ensure appropriate growth at the cellular and organismal level. In 
      Drosophila, the insulin receptor/TOR/S6K signaling network plays a fundamental 
      role in the control of metabolism and cell growth. Here we show that scylla and 
      charybdis, two homologous genes identified as growth suppressors in an EP 
      (enhancer/promoter) overexpression screen, act as negative regulators of growth. 
      The simultaneous loss of both genes generates flies that are more susceptible to 
      reduced oxygen concentrations (hypoxia) and that show mild overgrowth phenotypes. 
      Conversely, scylla or charybdis overactivation reduces growth. Growth inhibition 
      is associated with a reduction in S6K but not PKB/Akt activity. Together, genetic 
      and biochemical analysis places Scylla/Charybdis downstream of PKB and upstream 
      of TSC. Furthermore, we show that scylla and charybdis are induced under hypoxic 
      conditions and that scylla is a target of Drosophila HIF-1 (hypoxia-inducible 
      factor-1) like its mammalian counterpart RTP801/REDD1, thus establishing a 
      potential cross-talk between growth and oxygen sensing.
FAU - Reiling, Jan H
AU  - Reiling JH
AD  - Zoologisches Institut, Universitat Zurich, CH-8057 Zurich, Switzerland.
FAU - Hafen, Ernst
AU  - Hafen E
LA  - eng
PT  - Journal Article
DEP - 20041115
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Drosophila Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (chrb protein, Drosophila)
RN  - 0 (scyl protein, Drosophila)
RN  - EC 2.7.11.1 (Akt1 protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blotting, Western
MH  - Drosophila/*genetics
MH  - Drosophila Proteins/biosynthesis/chemistry/genetics/*physiology
MH  - Hypoxia/*metabolism
MH  - Molecular Sequence Data
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Sequence Homology, Amino Acid
PMC - PMC534649
EDAT- 2004/11/17 09:00
MHDA- 2005/04/02 09:00
PMCR- 2005/06/01
CRDT- 2004/11/17 09:00
PHST- 2004/11/17 09:00 [pubmed]
PHST- 2005/04/02 09:00 [medline]
PHST- 2004/11/17 09:00 [entrez]
PHST- 2005/06/01 00:00 [pmc-release]
AID - gad.322704 [pii]
AID - 00182879 [pii]
AID - 10.1101/gad.322704 [doi]
PST - ppublish
SO  - Genes Dev. 2004 Dec 1;18(23):2879-92. doi: 10.1101/gad.322704. Epub 2004 Nov 15.