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Ubiquitin-fusion degradation pathway plays key role in DNA vaccination.

Vaccine Weekly

| October 06, 2004 | COPYRIGHT 2004 NewsRX. This material is published under license from the publisher through the Gale Group, Farmington Hills, Michigan.  All inquiries regarding rights should be directed to the Gale Group. (Hide copyright information)Copyright

2004 OCT 6 - (NewsRx.com & NewsRx.net) -- The ubiquitin-fusion degradation pathway plays an indispensable role in naked DNA vaccination with a chimeric gene encoding a syngeneic cytotoxic T lymphocyte epitope of melanocyte and green fluorescent protein.

According to published research from Japan, "Antitumor immunity against murine melanoma B16 was achieved by genetic immunization with a naked chimeric DNA encoding a fusion protein linking green fluorescent protein (GFP) to the N-terminus of a major CD8+ cytotoxic T lymphocyte (CTL) epitope of tyrosinase-related protein 2 (TRP-2[subscript]181-188) of murine melanoma, designated as pGFP-TRP-2. Tumor growth was profoundly suppressed in C57BL/6 mice immunized with pGFP-TRP-2, while mice vaccinated with pTRP-2 showed rapid tumor growth and died within 40 days after tumor challenge. Splenocytes of mice immunized with pGFP-TRP-2 showed high CTL activity specific for TRP-2[subscript]181-188."

"GFP-TRP-2 expressed in COS-7 cells was rapidly degradated in vitro and the degradation was almost completely prevented by adding a proteasome inhibitor, MG-132, in the culture," said Manxin Zhang and collaborators at Kyushu University and the Tokyo Metropolitan Institute of Medical Science. "Furthermore, the antimelanoma immunity induced by genetic immunization with pGFP-TRP-2 was completely cancelled in mice deficient in proteasome activator PA28alpha/beta. Taken together, GFP-TRP-2 processed by cytosolic proteasome played a central role in breaking peripheral tolerance to a melanoma/melanocyte antigen, TRP-2[subscript]181-188, by activating CD8+ CTL specific for TRP-2[subscript]181-188."

"TRP-2[subscript]181-188 fused to GFP may be ...

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