PMID- 10567582
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20191217
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 12
DP  - 1999 Dec
TI  - Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain
      factor deltaEF1.
PG  - 8581-90
AB  - deltaEF1, a representative of the zinc finger-homeodomain protein family, is a
      transcriptional repressor which binds E2-box (CACCTG) and related sequences and
      counteracts the activators through transrepression mechanisms. It has been shown 
      that the N-proximal region of the protein is involved in the transrepression.
      Here we demonstrate that deltaEF1 has a second mechanism of transrepression
      recruiting CtBP1 or CtBP2 as its corepressor. A two-hybrid screen of mouse cDNAs 
      with various portions of deltaEF1 identified these proteins, which bind to
      deltaEF1 in a manner dependent on the PLDLSL sequence located in the short medial
      (MS) portion of deltaEF1. CtBP1 is the mouse orthologue of human CtBP, known as
      the C-terminal binding protein of adenovirus E1A, while CtBP2 is the second
      homologue. Fusion of mouse CtBP1 or CtBP2 to Gal4DBD (Gal4 DNA binding domain)
      made them Gal4 binding site-dependent transcriptional repressors in transfected
      10T1/2 cells, indicating their involvement in a transcriptional repression
      mechanism. When the MS portion of deltaEF1 was used to Gal4DBD and used to
      transfect cells, a strong transrepression activity was generated, but this
      activity was totally dependent on the PLDLSL sequence which served as the site
      for interaction with endogenous CtBP proteins, indicating that CtBP1 and -2 can
      act as corepressors. Exogenous CtBP1/2 significantly enhanced transcriptional
      repression by deltaEF1, and this enhancement was lost if the PLDLSL sequence was 
      altered, demonstrating that CtBP1 and -2 act as corepressors of deltaEF1. In the 
      mouse, CtBP1 is expressed from embryo to adult, but CtBP2 is mainly expressed
      during embryogenesis. In developing embryos, CtBP1 and CtBP2 are expressed
      broadly with different tissue preferences. Remarkably, their high expression
      occurs in subsets of deltaEF1-expressing tissues, e.g., cephalic and dorsal root 
      ganglia, spinal cord, posterior-distal halves of the limb bud mesenchyme, and
      perichondrium of forming digits, supporting the conclusion that CtBP1 and -2 play
      crucial roles in the repressor action of deltaEF1 in these tissues.
FAU - Furusawa, T
AU  - Furusawa T
AD  - Institute for Molecular and Cellular Biology, Osaka University, Osaka 565-0871,
      Japan.
FAU - Moribe, H
AU  - Moribe H
FAU - Kondoh, H
AU  - Kondoh H
FAU - Higashi, Y
AU  - Higashi Y
LA  - eng
SI  - GENBANK/AB033122
SI  - GENBANK/AB033123
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (ZEB1 protein, human)
RN  - 0 (Zfhx1a protein, mouse)
RN  - 0 (Zinc Finger E-box-Binding Homeobox 1)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.- (Ctbp2 protein, mouse)
RN  - EC 1.1.1.- (C-terminal binding protein)
SB  - IM
MH  - Alcohol Oxidoreductases
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - DNA, Complementary
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Embryonic and Fetal Development
MH  - Gene Expression
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - *Transcription Factors
MH  - Zinc Finger E-box-Binding Homeobox 1
MH  - *Zinc Fingers
PMC - PMC84984
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1128/mcb.19.12.8581 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Dec;19(12):8581-90. doi: 10.1128/mcb.19.12.8581.