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Zmpste24 is a mammalian integral membrane metalloproteinase that is critical for the processing of farnesylated proteins containing the carboxyl-terminal CAAX motif. Zmpste24, an ortholog of the yeast protein Ste24p, acts as an endoprotease by cleaving the 15 amino acids from the C terminus of prelamin A (including the farnesyl group), releasing mature lamin A.
INNOVATION: UCLA researchers have developed Zmpste24 knockout mice in order to determine the developmental and biochemical roll of Zmpste24. Zmpste24 -/- mice have retarded growth, hair loss, muscle weakness, spontaneous bone fracture, and shortened life spans. Zmpste24 deficient cells demonstrate the accumulation of wildtype farnesyl-prelamin A along the nuclear envelope, leading to misshapen nuclei. Researchers continue to utilize the Zmpste24 knockout mice to further understand the mechanism of progerias and ultimately provide treatment options for patients.
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Reference: UCLA Case No. 2007-222
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