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Researchers discover new form of cancer gene regulation

thway critical to early development of humans and animals involves the genes Sonic hedgehog (the signal) and GLI (the transcription factor).

The GLI family of three genes was first discovered in a human brain tumor, and mutations in this family of genes result in severe birth defects and devastating cancers in humans.

"While some cancers are explained by known defects in the regulation of the GLI1 gene, for many cancers the reasons for excessive GLI1 protein are not known. The protein levels and activity of GLI1 are likely regulated at levels other than the gene," Iannaccone said.

The form of regulation the researchers discovered occurs after the gene makes messenger RNA, the first step toward making a protein that controls cell fate. Once the messenger RNA leaves the cell, it participates in a process called translation, during which the cellular machinery makes a protein by linking amino acids together according to the plan described in the messenger RNA and thereby based on the information from the DNA sequence of the gene.

Iannaccone and colleagues showed that after the messenger RNA for GLI1 is made, it binds to the Quaking protein and inhibits the translation event. This means that all of the controls that the cell has on the gene for GLI1 can be present and active and the GLI1 is still not produced.

Significantly, the study demonstrated that this regulation is conserved from human to the worm, Caenorhabditis elegans (often used in laboratory research), indicating that the formation of these RNA protein complexes is a very ancient form of regulation of protein function.

Olga Lakiza, postdoctoral fellow in pediatrics at the Feinberg School, was the first author on the article. Iannaccone's other co-researchers on this study included David O. Walterhouse, associate professor of pediatrics, Feinberg School and Children's Memorial Research Center, and Elizabeth B. Goodwin, department of genetics, University of
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Source:Northwestern University


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