Genes Found That Label Cell Proteins For Disposal

proteins within cells are selected and "marked" for removal and destruction after they have done their job.

In their report published in the April 23 issue of the journal Molecular Cell, Xiong and his co-authors, Tomohiko Ohta, Jennifer J. Michel and Arndt J. Schottelius, describe having identified the proteins ROC1, ROC2 and APC11. These closely related proteins, particularly ROC1, combine with other proteins called cullins to form an enzyme, a ubiquitin ligase. This enzyme then accelerates a biochemical reaction in which a molecule called ubiquitin is attached to cellular proteins. Thus "ubiquitinized," the protein is marked for disposal and degradation. After degradation, the cell then recycles the protein's amino acids to build other proteins.

"Once a protein is attached to ubiquitin, another cellular mechanism recognizes that it's ubiquitinated and takes it to a specific place called the proteasome," Xiong points out. "It's like garbage collection. Unless you put your garbage out in the street, it won't get picked up and taken to the dump." In cells, the dumpsite is the proteasome's protein degradation machinery.

"Abnormal level of proteins, too high in the case of oncoproteins such as myc or cyclin D or too low in the case of tumor suppressor proteins such as p53, have one common consequence. They drive cells to continue proliferating when normal cells would not," Xiong says. "How these proteins in tumor cells escape from normal ubiquitin-mediated degradation is currently unknown."

Xiong and scientists elsewhere are working to solve this problem by identifying essential components involved in the normal control of protein degradation.

In their journal report, the UNC-CH researchers also note that the newly identified proteins can combine with five different cullins. "That means there are many binary ubiquitin ligases," Xiong says. "And it raises the possibility that degradation of different proteins may each require a differ

Contact: Lynn Wooten
University of North Carolina School of Medicine

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