Related Experiment Video

Updated: Sep 28, 2026

Isolation and Time-Lapse Imaging of Primary Mouse Embryonic Palatal Mesenchyme Cells to Analyze Collective Movement Attributes
07:13

Isolation and Time-Lapse Imaging of Primary Mouse Embryonic Palatal Mesenchyme Cells to Analyze Collective Movement Attributes

Published on: February 13, 2021

Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in

Umesh M Hanumegowda1, Vamsidhara C Dhulipala, Chada S Reddy

  • 1Department of Veterinary Biomedical Sciences, University of Missouri, W148 Vet Med Bldg, 1600 E Rollins, Columbia, Missouri 65211, USA.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|October 22, 2002
PubMed

Insights

Secalonic acid D (SAD), a mycotoxin, increases CREB phosphorylation but decreases its DNA binding, potentially causing cleft palate. SAD directly binds to phosphorylated CREB, inhibiting its function.

Area of Science:

  • Molecular Biology
  • Toxicology
  • Developmental Biology

Background:

  • Gene expression regulation involves CREB phosphorylation.
  • Secalonic acid D (SAD) is a mycotoxin linked to cleft palate (CP).
  • SAD induces CREB phosphorylation in palatal tissues.

Purpose of the Study:

  • Investigate the mechanisms behind SAD's effects on CREB.
  • Determine how SAD affects CREB phosphorylation and DNA binding.
  • Elucidate SAD's role in the development of cleft palate.

Main Methods:

  • Used palatal nuclear extracts (PNE) for in vitro studies.
  • Assessed CREB phosphorylation using cell culture and cell-free systems.
  • Analyzed TF-DNA binding and protein interactions via gel electrophoresis and binding assays.

Main Results:

  • SAD stimulates CREB phosphorylation via a novel kinase, independent of known inhibitors.
  • Increased phosphoCREB (pCREB) levels correlated with reduced TF binding to CRE.
  • SAD directly binds to pCREB, inhibiting its interaction with CRE sites, including the PCNA gene.

Conclusions:

  • SAD-induced CREB phosphorylation is mediated by a novel kinase.
  • SAD directly inhibits CREB DNA binding by binding to pCREB.
  • This mechanism may explain SAD's teratogenicity, leading to cleft palate by affecting cell proliferation.

More Related Videos

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis07:26

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis

Published on: April 1, 2022

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...