Article Abstract:
Research was conducted to examine the reconstitution of Sic1p ubiquitination with a set of purified proteins, including Cdc4p, Cdc53p and Skp1p and to show that Cdc4p, Cdc53p and Skp1p assemble into an E3 complex that selectively recognizes phosphorylated Sic1p through its Cdc4p and Skp1p subunits. Unfractionated inset cell lysates containing Cdc4p, ubiquitin and an ATP-regenerating system were mixed. Results indicate that phosphorylation-triggered ubiquitin-dependent proteolysis may be mediated by a conserved cullin-dependent pathway in eukaryotic cells.
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Article Abstract:
The crystal structure at 3.2 angstron unit resolution of one such protein, beta 2-chimaerin, a GTPase-activating protein for the small GTPase Rac, in its inactive conformation is reported. The structure shows that in the inactive state, the N terminus of beta2-chimaerin protrudes into the inactive site of the RacGAP domain, sterically blocking Rac binding.
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Article Abstract:
Muscle loss is due to accelerated protein breakdown through ubiquitin-dependent proteolysis. Genetic or pharmacological inhibition of IKKbeta/NF-kappaB/MuRF-1 pathway reversed muscle atrophy.
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