β-transducin repeat-containing protein (β-TrCP), one of the well-characterized F-box proteins, acts as a substrate receptor and constitutes an active SCFβ-TrCP E3 ligase with a scaffold protein CUL1, a RING protein RBX1, and an adaptor protein SKP1. β-TrCP plays a critical role in the regulation of various physiological and pathological processes, including signal transduction, cell cycle progression, cell migration, DNA damage response, and tumorigenesis, by governing burgeoning amounts of key regulators for ubiquitination and proteasomal degradation. Given that a variety of β-TrCP substrates are well-known oncoproteins and tumor suppressors, and dysregulation of β-TrCP is frequently identified in human cancers, β-TrCP plays a vital role in carcinogenesis. In this review, we first briefly introduce the characteristics of β-TrCP1, β-TrCP2, and SCFβ-TrCP ubiquitin ligase, and then discuss SCFβ-TrCP ubiquitin ligase regulated biological processes by targeting its substrates for degradation. Moreover, we summarize the regulation of β-TrCP1 and β-TrCP2 at multiple layers and further discuss the various roles of β-TrCP1 and β-TrCP2 in human cancer, functioning as either an oncoprotein or a tumor suppressor in a manner dependent of cellular context. Finally, we provide novel insights for future perspectives on the potential of targeting β-TrCP1 and β-TrCP2 for cancer therapy.
Keywords: CRL; Cullin-RING ligase; F-box protein; SCF; tumorigenesis; β-TrCP.
© 2020 Federation of European Biochemical Societies.