BASP1 is a transcriptional cosuppressor for the Wilms' tumor suppressor protein WT1.
The Wilms' tumor suppressor protein WT1 is a transcriptional regulator that plays a key role in the development of the kidneys. The transcriptional activation domain of WT1 is subject to regulation by a suppression region within the N terminus of WT1. Using a functional assay, we provide direct evidence that this requires a transcriptional cosuppressor, which we identify as brain acid soluble protein 1 (BASP1). WT1 and BASP1 associate within the nuclei of cells that naturally express both proteins. BASP1 can confer WT1 cosuppressor activity in transfection assays, and elimination of endogenous BASP1 expression augments transcriptional activation by WT1. BASP1 is present in the developing nephron structures of the embryonic kidney and, coincident with that of WT1, its expression is restricted to the highly specialized podocyte cells of the adult kidney. Taken together, our results show that BASP1 is a WT1-associated factor that can regulate WT1 transcriptional activity.
Carpenter
Brian
B
School of Biological Sciences, University of Manchester, G.186 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Hill
Kathryn J
KJ
Charalambous
Marika
M
Wagner
Kate J
KJ
Lahiri
Diya
D
James
Dominic I
DI
Andersen
Jens S
JS
Schumacher
Valérie
V
Royer-Pokora
Brigitte
B
Mann
Matthias
M
Ward
Andrew
A
Roberts
Stefan G E
SG
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016162:Genes, Wilms Tumor; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D025721:WT1 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C104089:BASP1 protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D025721:WT1 Proteins