The SCF complexes represent the largest family of ubiquitin-protein ligases and mediate the ubiquitination of a broad spectrum of regulatory and signalling proteins in diverse cellular pathways. The SCF consists of three invariant components, Skp1, Cul1, and Rbx1 and an interchangeable subunit, an F-box protein which is responsible for recruiting specific substrates to be ubiquitinated by the SCF. SCFFbw7 mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell division, growth and differentiation, including Cyclin E1, c-Myc, Notch and c-Jun. Mutations have been found in the Fbw7 subunit of SCFFbw7 in various types of human cancers, therefore Fbw7 is considered to be a potent tumor suppressor.
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