%0 Journal Article
%T Wt-1 Expression Linked to Nitric Oxide Availability during Neonatal Obstructive Nephropathy
%A Luciana Mazzei
%A Walter Manucha
%J Advances in Urology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/401750
%X The wt-1 gene encodes a zinc finger DNA-binding protein that acts as a transcriptional activator or repressor depending on the cellular or chromosomal context. The wt-1 regulates the expression of a large number of genes that have a critical role in kidney development. Congenital obstructive nephropathy disrupts normal renal development and causes chronic progressive interstitial fibrosis, which contributes to renal growth arrest, ultimately leading to chronic renal failure. Wt-1 is downregulated during congenital obstructive nephropathy, leading to apoptosis. Of great interest, nitric oxide bioavailability associated with heat shock protein 70 (Hsp70) interaction may modulate wt-1 mRNA expression, preventing obstruction-induced cell death during neonatal unilateral ureteral obstruction. Moreover, recent genetic researches have allowed characterization of many of the complex interactions among the individual components cited, but the realization of new biochemical, molecular, and functional experiments as proposed in our and other research labs allows us to establish a deeper level of commitment among proteins involved and the potential pathogenic consequences of their imbalance. 1. Wt-1 Expression and Isoforms The wt-1 gene encodes a zinc finger DNA-binding protein that acts as a transcriptional activator or repressor depending on the cellular or chromosomal context. Wilms tumor locus was narrowed down to a region of less than 345£¿kb on human chromosome 11p13. The wt-1 mRNA has three translation start sites resulting in three isoforms of the protein with different molecular weights: 62¨C64£¿kDa, 52¨C54£¿kDa, and 36¨C38£¿kDa. Typical protein WT-1 is 52¨C54£¿kDa isoform [1]. In addition, it has 4 major isoforms, due to the insertion of 3 amino acids (KTS) between zinc fingers 3 and 4 and the insertion of an alternatively spliced 17-amino acid segment encoded by exon 5 in the middle of the protein [2]. Florio et al. stated that at least 24 different WT-1 isoforms are produced by alternative splicing and the use of alternate translation initiation sites [3]. Previously, Scharnhorst et al. described additional WT-1 isoforms with distinct transcription-regulatory properties, indicating further the complexity of WT-1 expression and activity. They stated that 32 WT-1 protein forms had been described [4]. The 429-amino acid polypeptide had features suggesting a role in transcriptional regulation: the presence of 4 zinc finger domains and a region rich in proline and glutamine. The conservation in structure and relative levels of the 4£¿wt-1 mRNA species suggests that
%U http://www.hindawi.com/journals/au/2013/401750/