Entrez Gene

General information | Expression | Regulation | Mutation | Interaction

Basic Information
Gene ID	231
Name	AKR1B1
Synonymous	ADR\|ALDR1\|ALR2\|AR;aldo-keto reductase family 1, member B1 (aldose reductase);AKR1B1;aldo-keto reductase family 1, member B1 (aldose reductase)
Definition	Lii5-2 CTCL tumor antigen\|aldehyde reductase 1\|aldo-keto reductase family 1 member B1\|aldose reductase\|low Km aldose reductase
Position	7q35
Gene type	protein-coding
Source	Count: 1; Generif
Sentence	Abstract
Aldose reductase gene was identified in the genome-wide loss-of-function genetic screen as putative tumor suppressor located at 7q35.	Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. To identify new senescence regulatory genes that might play a role in tumorigenesis, we have designed and performed a large-scale antisense-based genetic screen in primary mouse embryo fibroblasts (MEFs). Out of this screen, we have identified five different genes through which loss of function partially bypasses senescence. These genes belong to very different biochemical families: csn2 (component of the Cop9 signalosome), aldose reductase (a metabolic enzyme) and brf1 (subunit of the RNA polymerase II complex), S-adenosyl homocysteine hydrolase and Bub1. Inactivation, at least partial, of these genes confers resistance to both p53- and p16INK4a-induced proliferation arrest. Furthermore, such inactivation inhibits p53 but not E2F1 transcriptional activity and impairs DNA-damage-induced transcription of p21. Since the aim of the screen was to identify new regulators of tumorigenesis, we have tested their inactivation in human tumors. We have found, either by northern blot or quantitative reverse transcriptase-PCR analysis, that the expression of three genes, Csn2, Aldose reductase and Brf1, is lost at different ratios in tumors of different origins. These genes are located at common positions of loss of heterogeneity (15q21.2, 7q35 and 14q32.33); therefore,we have measured genomic losses of these specific genes in different tumors. We have found that Csn2 and Brf1 also show genomic losses of one allele in different tumors. Our data suggest that the three genes identified in the genome-wide loss-of-function genetic screen are putative tumor suppressors located at 15q21.2; 7q35 and 14q32.33.