PMID- 11354513
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20051117
IS  - 0270-4145 (Print)
IS  - 0270-4145 (Linking)
VI  - 20
IP  - 4
DP  - 2000 Oct-Dec
TI  - Secalonic acid D alters the expression and phosphorylation of the transcription 
      factors and their binding to cAMP response element in developing murine secondary 
      palate.
PG  - 173-82
AB  - Secalonic acid D (SAD), a cleft palate-inducing mycotoxin, reduces palatal cyclic 
      AMP (cAMP) levels. cAMP relays its signals via the transcription factors (TF) 
      such as cAMP response element (CRE) binding protein (CREB), CRE modulator (CREM) 
      and activator transcription factor-1 (ATF-1) to CRE-containing genes. These 
      studies tested the hypothesis that these TF are present and functional in the 
      developing palate and that SAD alters their expression and function along with 
      that of the CRE-containing gene, proliferating cell nuclear antigen (PCNA). 
      Electrophoretic mobility shift assays (EMSA), using nuclear extracts of control 
      and SAD-treated developing palate tissues and 32P-labeled CRE revealed the 
      formation of a DNA-protein complex. Supershift/ablation assays with TF antibodies 
      showed the presence of CREB, CREM and another unidentified TF but not ATF-1 in 
      the complex. Western analyses of the DNA-protein complex from preparative EMSA 
      revealed increased binding of CREB to CRE in direct correlation with increase in 
      phospho-CREB (pCREB) in the controls. Exposure to SAD significantly reduced CREB 
      binding throughout palate development. This was in correlation with reductions in 
      pCREB levels on gestational day (GD) 13 and 14 palates. On GD 12, however, SAD 
      dramatically increased CREB phosphorylation. The ontogeny of palatal CREB and 
      CREM (several isoforms) expression remained unchanged in controls whereas SAD 
      increased that of the repressor isoform of CREM. The expression of PCNA was 
      inhibited by SAD on GD 12. These results show that the cAMP signaling pathway is 
      functional in the palate and that SAD alters CREB phosphorylation and inhibits 
      its binding to CRE. leading to altered expression of genes involved in cell 
      proliferation, an event critical for normal palate development.
FAU - Umesh, H
AU  - Umesh H
AD  - Department of Veterinary Biomedical Sciences, University of Missouri, Columbia, 
      USA.
FAU - Ganesh, B
AU  - Ganesh B
FAU - Reddy, C S
AU  - Reddy CS
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - J Craniofac Genet Dev Biol
JT  - Journal of craniofacial genetics and developmental biology
JID - 8109845
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Mycotoxins)
RN  - 0 (Transcription Factors)
RN  - 0 (Xanthenes)
RN  - 0 (Xanthones)
RN  - 56283-72-8 (secalonic acid)
SB  - IM
MH  - Animals
MH  - Cyclic AMP Response Element-Binding Protein/*physiology
MH  - Mice
MH  - Mycotoxins/pharmacology
MH  - Palate/embryology/*physiology
MH  - Phosphorylation
MH  - Protein Binding
MH  - Signal Transduction/*drug effects
MH  - Transcription Factors/*physiology
MH  - Xanthenes/*pharmacology
MH  - *Xanthones
EDAT- 2001/05/17 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/05/17 10:00
PHST- 2001/05/17 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/05/17 10:00 [entrez]
PST - ppublish
SO  - J Craniofac Genet Dev Biol. 2000 Oct-Dec;20(4):173-82.