High impact information on RNF111

• Additional modulators of Nodal signaling include convertases that regulate the generation of the mature signal, and factors such as Arkadia and DRAP1 that regulate the cellular responses to the signal [1].
• Arkadia dorsalizes ventral tissues, resulting in the induction of organizer-specific gene expression [2].
• The combined activities of Arkadia and Xenopus nodal-related-1 are sufficient to induce mesendoderm and suppress mesoderm [2].
• Our findings, together with the observation that Arkadia mutant mice lack a node and node-derived mesendoderm, identify Arkadia as an essential modulator of the nodal signalling cascade that leads to induction of Spemann's organizer [2].
• Arkadia (Akd) was discovered by mouse gene-trap mutagenesis and encodes a nuclear E3 ubiquitin ligase [3].

Biological context of RNF111

• We have employed bioinformatics and developed a reporter system to address Akd post-transcriptional regulation [3].
• Akd RNA may initiate from different promoters and 5' UTR differential splicing, upstream AUGs (uAUGs) and open-reading frames upstream (uORFs) may regulate protein translation [3].
• These data may represent mechanisms by which translational control of Arkadia is achieved and ultimately how TGF-beta/Nodal signalling is regulated during embryogenesis [3].

Regulatory relationships of RNF111

• Therefore, the activation of Smad signalling induced by TGF-beta(1) plays a key role in the mechanism of renal tubular EMT, and in this process, Arkadia may has an important influence on the mechanism above mentioned through degradation of Smad7 [4].

References