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U-M scientists see ubiquitin-modified proteins in living cells

ANN ARBOR, Mich. Researchers at the University of Michigan Medical School and Howard Hughes Medical Institute have found a way to see proteins in cells that have been tagged by a molecular "sticky note" called ubiquitin.

"This technology allows us to see, under a microscope, proteins modified by ubiquitin inside the cell," says Tom K. Kerppola, Ph.D., an associate professor of biological chemistry in the Medical School and an HHMI associate investigator. "Visualization gives us a direct connection to cellular processes that we could only study in test tubes or indirectly before."

In a paper published online this week in the early edition of the Proceedings of the National Academy of Sciences, Kerppola and Deyu Fang, M.D., Ph.D., a U-M research investigator, describe the first use of a technology called ubiquitin-mediated fluorescence complementation to study a cell-signaling mechanism called ubiquitination.

In this process, a small peptide called ubiquitin is linked to a protein in ways that can change the protein's function and location within the cell. Originally, scientists thought ubiquitin was simply a universal "destroy me" signal for unneeded or harmful proteins, but it has recently been found to be associated with many other cellular functions.

"The same ubiquitin signal can cause one protein to be degraded, but another protein to be moved to a new location," Kerppola says. "We're interested in learning how this works."

In their PNAS paper, Kerppola and Fang describe how ubiquitin latched onto Jun - a protein involved in cell growth and gene transcription and moved Jun from its usual location in the cell's nucleus into hollow spheres called lysosomes in the cytoplasm outside the nucleus. Filled with digestive enzymes, lysosomes break down unwanted proteins into amino acids the cell recycles to make new proteins.

"Jun's function in the nucleus is transient and time-dependent," Kerppola sa
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Contact: Sally Pobojewski
pobo@umich.edu
734-615-6912
University of Michigan Health System
7-Oct-2004


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