The many faces of the E3 ubiquitin ligase, RNF220, in neural development and beyond

Abstract

Protein ubiquitination, an important posttranslational modification, is involved in almost all biological processes in eukaryotes (Zheng & Shabek, 2017). During embryonic development, protein ubiquitination plays a critical role in controlling signaling pathways that are essential for developmental patterning and determination of cell fate (Rape, 2017). Ubiquitination of target proteins is catalyzed by a three-step enzymatic cascade, including E1 ubiquitin-activating, E2 ubiquitin-conjugating, and E3 ubiquitin-ligating enzymes (Pickart, 2001). Ubiquitin has seven lysine (K) residues (K6, K11, K27, K29, K33, K48, and K63) that are involved in the formation polyubiquitin chains of different linkage types. Different linked polyubiquitin chains invoke various functional outcomes specific for each target protein. The most abundant polyubiquitin chains are K48-and K63linked chains, where the K48-linked chains function as a signal for

The RNF220 domain nuclear factor Teyrha-Meyrha (Tey) regulates the migration and differentiation of specific visceral and somatic muscles inDrosophila

“…S1). Hence, it is questionable whether the C-terminal domain of Tey is able to mediate ubiquitin ligase activity, as has been reported for mouse RNF220 (Ma et al, 2019; Song et al, 2020; Ma and Mao, 2022). However, Drosophila has a paralog of Tey of largely unknown function, CG4813 (recently renamed Drosophila RNF220; Sferra et al, 2021), which features a complete RING domain in addition to its RNF220 domain, and in Tenebrio , both paralogs have a complete RING domain (Fig.…”

“…Like Tey, murine RNF220 is expressed in neuronal tissues of the CNS, but unlike Tey it is not known to be expressed in developing muscle tissues. In various neuronal contexts, murine RNF220 has been documented to mono- or poly-ubiquitinate several transcription factors, chromatin regulators, and nuclear effectors of the Wnt and Sonic Hedgehog pathways (reviewed in Ma and Mao, 2022). For some of these factors, RNF220-dependent ubiquitination has activating or stabilizing effects whereas for others it leads to their inactivation or degradation (Ma and Mao, 2022).…”

“…In various neuronal contexts, murine RNF220 has been documented to mono- or poly-ubiquitinate several transcription factors, chromatin regulators, and nuclear effectors of the Wnt and Sonic Hedgehog pathways (reviewed in Ma and Mao, 2022). For some of these factors, RNF220-dependent ubiquitination has activating or stabilizing effects whereas for others it leads to their inactivation or degradation (Ma and Mao, 2022). Many of these functions require the RNF220 binding partner ZC4H2 (a C4H2-type zinc finger protein) and mutations in the genes for the two proteins cause similar neuronal phenotypes (Ma and Mao, 2022).…”

“…For some of these factors, RNF220-dependent ubiquitination has activating or stabilizing effects whereas for others it leads to their inactivation or degradation (Ma and Mao, 2022). Many of these functions require the RNF220 binding partner ZC4H2 (a C4H2-type zinc finger protein) and mutations in the genes for the two proteins cause similar neuronal phenotypes (Ma and Mao, 2022). Interestingly, two independent large-scale protein interaction screens found the Drosophila ortholog of ZC4H2, CG13001, to bind to the paralog of Tey, CG4813 (Guruharsha et al, 2011; Hu et al, 2017), which may indicate that some of the molecular functions of murine and Drosophila RNF220 proteins are shared.…”

The E3 ubiquitin ligase RNF220 maintains hindbrainHoxexpression patterns through regulation of WDR5 stability

“…RNF220 is an E3 ubiquitin ligase widely involved in neural development through targeting a range of proteins (Kim et al ., 2018; Kong et al ., 2010; Pengcheng Ma & Mao, 2021; Pengcheng Ma et al ., 2022; Y.-B. Wang et al ., 2022.)…”