S-phase Kinase-Associated Protein 1 (SKP1) is a crucial component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex. This complex plays a significant role in the ubiquitination and subsequent proteasomal degradation of various protein substrates, which is essential for regulating numerous cellular processes, including cell cycle progression, signal transduction, and transcription .
SKP1 serves as an adaptor protein within the SCF complex, linking the F-box protein to CUL1. The F-box proteins are responsible for recognizing specific substrates that need to be ubiquitinated. This interaction is vital for the poly-ubiquitination of target proteins, marking them for degradation by the 26S proteasome .
The SCF complex, with SKP1 as a core component, is involved in maintaining genome stability by regulating pathways such as DNA damage repair, apoptotic signaling, and centrosome dynamics. Aberrant expression or dysfunction of SKP1 and the SCF complex can lead to disruptions in these pathways, potentially contributing to the development of diseases like cancer .
Human recombinant SKP1 Isoform A is typically produced using recombinant DNA technology. The gene encoding SKP1 is cloned into an expression vector, which is then introduced into a suitable host cell, such as Escherichia coli or mammalian cells. The host cells express the SKP1 protein, which is subsequently purified using various chromatographic techniques to obtain the recombinant protein in its active form .
SKP1 interacts with various F-box proteins, each recognizing different substrates for ubiquitination. This interaction is crucial for the SCF complex’s function in targeting specific proteins for degradation. The ubiquitination process involves the transfer of ubiquitin molecules to the lysine residues of the target protein, a reaction catalyzed by the E3 ubiquitin ligase activity of the SCF complex .
Alterations in SKP1 expression or function can have significant pathological implications. For instance, overexpression or mutations in SKP1 have been linked to various cancers due to the resulting genome instability and disrupted cellular processes. Understanding these alterations can provide insights into cancer pathogenesis and potentially identify SKP1 as a therapeutic target .