PMID- 10529426
OWN - NLM
STAT- MEDLINE
DCOM- 19991217
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 126
IP  - 22
DP  - 1999 Nov
TI  - The subcellular localization and activity of Drosophila cubitus interruptus are
      regulated at multiple levels.
PG  - 5097-106
AB  - Cubitus interruptus (Ci), a Drosophila transcription factor, mediates Hedgehog
      (Hh) signaling during the patterning of embryonic epidermis and larval imaginal
      discs. In the absence of Hh signal, Ci is cleaved to generate a truncated nuclear
      form capable of transcriptional repression. Hh signaling stabilizes and activates
      the full-length Ci protein leading to strong activation of downstream target
      genes including patched and decapentaplegic. A number of molecules have been
      implicated in the regulation of Ci. Mutations in these molecules lead to changes 
      in Ci protein level, the extent of Ci proteolysis and the expression of Ci target
      genes. This paper examines the regulation of Ci subcellular localization and
      activity. We first characterize a bipartite nuclear localization signal (NLS)
      within Ci. We propose that the subcellular distribution of Ci is affected by two 
      opposing forces, the action of the NLS and that of at least two regions targeting
      Ci to the cytoplasm. Further our data show that loss of PKA or Costal-2 activity 
      does not fully mimic Hh signaling, demonstrating that Ci proteolysis and Ci
      activation are two distinct events which are regulated through different paths.
      Finally, we propose that there are three levels of apparent Ci activity,
      corresponding to three zones along the AP axis with different sets of gene
      expression and different levels of Hh signaling.
FAU - Wang, Q T
AU  - Wang QT
AD  - Department of Biochemistry, Molecular Biology and Cell Biology, Robert H. Lurie
      Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA.
FAU - Holmgren, R A
AU  - Holmgren RA
LA  - eng
GR  - GM057450/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Insect Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Transcription Factors)
RN  - 0 (ci protein, Drosophila)
RN  - 0 (cos protein, Drosophila)
RN  - 149291-21-4 (hh protein, Drosophila)
RN  - EC 2.7.1.- (fu protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - Conserved Sequence
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism/physiology
MH  - Cysteine Endopeptidases/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Drosophila Proteins
MH  - Drosophila melanogaster/metabolism
MH  - Genes, Reporter
MH  - Hedgehog Proteins
MH  - Insect Proteins/physiology
MH  - Kinesins/genetics
MH  - Multienzyme Complexes/metabolism
MH  - Nuclear Localization Signals
MH  - Nuclear Proteins/*metabolism
MH  - Phosphorylation
MH  - Proteasome Endopeptidase Complex
MH  - Protein Isoforms/metabolism
MH  - Protein Serine-Threonine Kinases/genetics
MH  - Signal Transduction
MH  - Subcellular Fractions
MH  - Transcription Factors
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1242/dev.126.22.5097 [doi]
PST - ppublish
SO  - Development. 1999 Nov;126(22):5097-106. doi: 10.1242/dev.126.22.5097.