Bcl-3 Shown to Block the Ubiquitination Pathway

A recent report described how the regulatory protein Bcl-3 (B cell leukemia-3) regulated the inflammatory response by blocking the ubiquitination pathway.

In order to study Bcl-3's mode of action investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA) genetically engineered a line of mice that lacked the gene for Bcl-3.

Results published in the August 3, 2007, edition of Science revealed that Bcl-3 interacted with p50, a protein that inhibits gene transcription by binding to DNA. Normally p50 suppressed the DNA region coding for inflammation, halting the response to infection. However, p50 was unable to impede the inflammation response, as ubiquitination degraded it very fast. When the ubiquitination pathway in the Bcl-3–deficient mice was blocked, their cells were hypersensitive and unable to control responses to inflammatory substances.

"Our study identifies another layer of information that controls the inflammatory response,” said senior author Dr. Youhai Chen, associate professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine. "Bcl-3 appears to take in information from the body and, in response to infection, interferes with p50 degradation to decrease inflammatory response. Inflammation is natural. If we did not respond to infectious agents, bacteria would kill us. However, the inflammatory response must be controlled or we could also die. Bcl-3 helps regulate inflammation.”


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Pennsylvania School of Medicine