betaTrCP1

BetaTrCP1, also known as beta-transducin repeat-containing protein 1, is a human protein encoded by the BTRC gene. It is a member of the F-box/WD40-repeat protein family and functions as a substrate receptor in the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex. The protein contains an N-terminal F-box domain that binds SKP1 and a C-terminal WD40-repeat propeller that recognizes substrates. Substrate binding typically requires phosphorylation to create a degron motif such as DSGxxS, which is recognized by the WD40 domain.

Biological roles of betaTrCP1 include targeting a range of phosphorylated substrates for ubiquitination and proteasomal degradation. Classic substrates include IκBα, whose degradation activates NF-κB signaling, and β-catenin, whose degradation restrains the canonical Wnt pathway. Other substrates include Emi1, REST, and CDC25A, linking betaTrCP1 to cell cycle control and DNA damage responses. Through these actions, betaTrCP1 participates in regulation of inflammation, development, cell proliferation, and genomic stability.

Genetics and paralogs: The human genome encodes two β-TrCP proteins, β-TrCP1 (BTRC) and β-TrCP2 (encoded by FBXW11), which share substantial sequence similarity and overlapping substrate repertoires. They can function redundantly in many contexts.

Clinical significance: Altered betaTrCP1 activity or expression has been associated with cancer and inflammatory disorders. Depending on substrate context, β-TrCP1 can act as a tumor promoter or tumor suppressor. Because of its central role in degrading multiple signaling regulators, components of the SCFβ-TrCP complex are of interest in therapeutic strategies.