SKP1

SKP1 Full Name

S-phase kinase-associated protein 1

SKP1 Introduction

SKP1 (S-phase kinase-associated protein 1) is a central component of the SCF (SKP1–Cullin–F-box) E3 ubiquitin ligase complex, which orchestrates the targeted ubiquitination and proteasomal degradation of numerous regulatory proteins involved in cell cycle control, signal transduction, and DNA damage response. By serving as a critical adaptor linking Cullin-1 to diverse F-box proteins, SKP1 enables the SCF complex to recognize a wide spectrum of substrates, thereby maintaining precise cellular homeostasis. Its structural flexibility, particularly within intrinsically disordered regions, allows SKP1 to accommodate various F-box proteins, highlighting its molecular adaptability and central role in modulating protein turnover across multiple signaling pathways.

Functionally, SKP1 is essential for genome integrity and chromosome stability. Aberrant expression or functional disruption of SKP1 has been linked to impaired DNA damage repair, centrosome abnormalities, and chromosomal instability (CIN), all of which can drive tumorigenesis. Beyond its canonical role in protein ubiquitination, SKP1 homologs in model organisms, such as C. elegans, also contribute structurally to meiotic chromosome scaffolding and synaptonemal complex assembly, revealing "moonlighting" functions that are independent of SCF-mediated proteolysis. These findings underscore the dual regulatory and structural roles of SKP1 in maintaining proper cell division and genetic fidelity.

Clinically, altered SKP1 expression is frequently observed across a wide range of human cancers, with patterns of both overexpression and downregulation depending on tumor type. Somatic copy number variations and mutations in SKP1 are associated with disrupted cell cycle regulation, enhanced chromosomal instability, and poor prognosis in several malignancies. These characteristics position SKP1 as a promising prognostic biomarker and potential therapeutic target, particularly for strategies aiming to restore genome stability or selectively exploit vulnerabilities in cancer cells with SCF complex dysfunction. The emerging insights into SKP1's multifaceted roles continue to fuel translational research for novel anti-cancer interventions.

Alternate Names for SKP1

SKP1; S-phase kinase-associated protein 1; OCP2; p19A; EMC19; SKP1A; OCP-II; TCEB1L; SIII; OCP-2

• 1.Thompson LL, et al.; Aberrant SKP1 Expression: Diverse Mechanisms Impacting Genome and Chromosome Stability. Front Cell Dev Biol. 2022, 10:859582.
  2.Thompson LL, et al.; The SCF Complex Is Essential to Maintain Genome and Chromosome Stability. Int J Mol Sci. 2021, 22(16):8544.