F-box proteins in epigenetic regulation of cancer

Abstract

Epigenetic abnormalities are now realized as important as genetic alterations in contributing to the initiation and progression of cancer. Recent advancements in the cancer epigenetics field have identified extensive alterations of the epigenetic network in human cancers, including histone modifications and DNA methylation. F-box proteins, the substrate receptors of SCF (SKP1-Cullin1-F-box protein) E3 ubiquitin ligases, can directly and indirectly affect the balance of epigenetic regulation. In this brief review, we discuss our current understanding of F-box proteins in cellular epigenetic regulation and how dysregulation of these processes contribute to cancer development.

KDM2A/B lysine demethylases and their alternative isoforms in development and disease

“…Interestingly, the KDM2B PHD domain also exhibits an E3 ubiquitin ligase activity [59]. KDM2A and KDM2B are the only members of the JmjC family that contain a C-terminal F-box domain [48,[92][93][94]. As opposed to the KDM2A F-box domain, whose function is still elusive, the KDM2B F-box domain has been shown to mediate protein-protein interactions.…”

“…Although the JmjC domain of JARID2, a member of the JmjC domain-containing protein family, is not active due to amino acid substitutions in comparison to catalytically active JARID1, its loss-of-function phenotype is embryonically lethal and JARID2 is essential for early development [127]. On the other hand, FBXL19, a member of the F-box family proteins resembles KDM2A/B-SF since it contains the CXXC, PHD, F-box and LRR domains, but completely lacks the JmjC demethylase domain [48,93,94,128]. Despite lacking demethylation activity, FBXL19 plays an important role as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex [93,94], and it has recently been shown to be essential for mouse development [128].…”

A novel F‐box domain containing cyclin F like gene is required for maintaining the genome stability and survival of chicken primordial germ cells

“…45 However, the F-box domain is not only limited to cyclin F, but identified in a number of proteins in budding yeast and vertebrate species. 48,49 Studies have shown that either working in concert with the SCF complex or alone, F-box proteins function in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. 47 The F-box proteins have the ability to control the degradation of several crucial proteins associated with drug resistance, and dysregulation of these proteins contribute to cancer development.…”

“…47 The F-box proteins have the ability to control the degradation of several crucial proteins associated with drug resistance, and dysregulation of these proteins contribute to cancer development. 48,49 Studies have shown that either working in concert with the SCF complex or alone, F-box proteins function in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. 50 Cyclin F is one of the several classes of cyclins identified continuously since 1983, 51 and they fall into classes based on their structural similarity, timing of expression and functional points within the cell cycle.…”

Pediococcus acidilactici P25 Protected Caenorhabditis elegans against Enterotoxigenic Escherichia coli K88 Infection and Transcriptomic Analysis of Its Potential Mechanisms

“…Clec-39 and Clec-49 protein-deficient nematodes became sensitive to Serratia marcescens infection [69]. F-box proteins (FBPs) contribute to cell proliferation, cycle, apoptosis, migration, invasion, metastasis [70,71], and antiretroviral function [72,73].…”