The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development

Madhulika Sharma1, Jennifer G Brantley, Dianne Vassmer

  • 1Department of Anatomy, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. msharma3@kumc.edu

Gene
|April 1, 2009
PubMed

Insights

The homeodomain protein Cux1 interacts with Grg4 to repress p27(kip1) gene expression, a key process in kidney development. This interaction is crucial for regulating cell proliferation in the developing kidney.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • The homeodomain protein Cux1 is vital for regulating cell proliferation in the developing kidney's nephrogenic zone.
  • Notch signaling plays a critical role in kidney development, with Grg4 (Groucho 4) as a known effector.

Purpose of the Study:

  • To investigate the interaction between Cux1 and Grg4.
  • To elucidate the mechanism by which Cux1 regulates p27(kip1) gene expression during kidney development.

Main Methods:

  • Promoter reporter luciferase assays to assess p27(kip1) promoter activity.
  • Chromatin immunoprecipitation (ChIP) assays to detect in vivo interactions.
  • DNAse1 footprinting to identify Cux1 binding sites on the p27(kip1) promoter.

Main Results:

  • Cux1 directly interacts with the co-repressor Grg4.
  • Cux1 and Grg4 enhance the repression of p27(kip1) promoter activity.
  • Cux1, Grg4, HDAC1, and HDAC3 bind to the p27(kip1) promoter in vivo.
  • Cux1 binds to specific sequences on the p27(kip1) promoter.

Conclusions:

  • Grg4 is identified as a novel interacting partner for Cux1.
  • A mechanism for p27(kip1) repression by Cux1 during kidney development is proposed, involving Grg4 and histone deacetylases.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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...