The utility F-box for protein destruction

Abstract

A signature feature of all living organisms is their utilization of proteins to construct molecular machineries that undertake the complex network of cellular activities. The abundance of a protein element is temporally and spatially regulated in two opposing aspects: de novo synthesis to manufacture the required amount of the protein, and destruction of the protein when it is in excess or no longer needed. One major route of protein destruction is coordinated by a set of conserved molecules, the F-box proteins, which promote ubiquitination in the ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. We particularly emphasize the mechanisms whereby F-box proteins recruit specific substrates and regulate their abundance in the context of SCF E3 ligases. For some exceptions, we also review how F-box proteins function through non-SCF mechanisms.

Arabidopsis Kelch Repeat F-Box Proteins Regulate Phenylpropanoid Biosynthesis via Controlling the Turnover of Phenylalanine Ammonia-Lyase

“…The cytokinin signaling cascade has a central role in regulating cell division; it also modulates the development of the shoots and roots and stress responses (Sakakibara, 2006). F-box proteins can selectively target a set of substrates (Craig and Tyers, 1999;del Pozo and Estelle, 2000;Gagne et al, 2002;Risseeuw et al, 2003;Ho et al, 2008). The alteration of phenylpropanoid-lignin biosynthesis, along with the disturbance of KFB gene expression, is unlikely attributable to the changes in Arabidopsis response regulator stability and the cytokinin response, since, for example, the reduction of the levels of phenolics and lignin in the KFB overexpression lines is not due to the downregulation of PAL transcription but to the decrease in enzyme concentration (Figures 10 and 11).…”

The genome of pseudocowpoxvirus: comparison of a reindeer isolate and a reference strain

“…The ORFV ANK/F-box proteins (ORFs 008,123,126,128 and 129) have been shown to be functionally active, interacting with components of the cellular SCF ubiquitin ligase complex via their F-box-like domains (Sonnberg et al, 2008). Cellular F-box proteins facilitate protein degradation via the ubiquitin-proteasome pathway (Ho et al, 2008;Zhang et al, 2009), raising the possibility that poxvirus ANK/F-box proteins direct the removal of unwanted host cell proteins in order to favour viral replication. Inhibitory roles in ubiquitination pathways are also possible (Mercer et al, 2005;Sonnberg et al, 2008;Zhang et al, 2009).…”

An E3 ligase complex regulates SET-domain polycomb group protein activity in Arabidopsis thaliana

“…The system degrades abnormal proteins that are produced by biosynthetic errors or have folded into nonnative conformations. It also controls the level of specific regulatory proteins that control cell cycle progression, signal transduction, gene transcription, programmed cell death, and development in animals as well as hormone synthesis and signaling, plant-pathogen interactions, self-incompatibility, circadian rhythms, morphogenesis, and histone modifications in plants (10)(11)(12). A well-characterized E3 ligase, SCF, is composed of multiple subunits: a CULLIN1 (CUL1) scaffold protein; a catalytic RING domain protein, RING-BOX1 (RBX1); an adaptor protein called S-PHASE KINASE-ASSOCIATED PROTEIN1 (SKP1) in animals and ARABIDOPSIS SKP1 HOMOLOG1/2 (ASK1/2) in Arabidopsis; and an F-box protein, which confers substrate specificity in the transfer of ubiquitin from the E2 ubiquitin-conjugating enzyme to the target protein.…”