BASP1 is a transcriptional cosuppressor for the Wilms' tumor suppressor protein WT1

Brian Carpenter1, Kathryn J Hill, Marika Charalambous

  • 1School of Biological Sciences, University of Manchester, G.186 Stopford Building, Oxford Road, Manchester M13 9PT, UK.

Insights

Brain acid-soluble protein 1 (BASP1) acts as a crucial cosuppressor for the Wilms' tumor suppressor protein (WT1). This discovery reveals a new regulatory mechanism in kidney development and WT1 transcriptional activity.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The Wilms' tumor suppressor protein (WT1) is a critical transcriptional regulator in kidney development.
  • WT1's transcriptional activation is modulated by an N-terminal suppression region.

Purpose of the Study:

  • To identify the factors involved in WT1-mediated transcriptional repression.
  • To elucidate the role of novel interacting proteins in WT1 function.

Main Methods:

  • Functional assays to test for cosuppressor activity.
  • Co-immunoprecipitation to assess protein-protein interactions.
  • Transfection assays to evaluate regulatory effects.
  • Immunohistochemistry to determine protein localization in embryonic and adult kidneys.

Main Results:

  • Brain acid-soluble protein 1 (BASP1) was identified as a WT1 transcriptional cosuppressor.
  • WT1 and BASP1 form nuclear complexes in cells expressing both proteins.
  • BASP1 expression is required for WT1 cosuppressor activity; its elimination enhances WT1 activation.
  • BASP1 is localized in developing nephrons and adult podocytes, mirroring WT1 expression patterns.

Conclusions:

  • BASP1 is a key WT1-associated factor that regulates WT1 transcriptional activity.
  • BASP1 plays a significant role in the biological functions of WT1, particularly in kidney development.

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...