Phosphorylation of Junb family proteins by the Jun N-terminal kinase supports tissue regeneration in zebrafish

Tissue regeneration is fundamental for multi-cellular organisms to maintain their integrity, but the competence of tissue restoration is different depending on tissues, species, and ages. In spite of the recent progresses of the molecular basis of regeneration, little is known about its regulative processes. We previously identified the junb and junb-like (junbl) as transcripts induced in response to tissue injury in zebrafish. It has been demonstrated that the mammalian JunB is not phosphorylated by the Jun N-terminal kinase (JNK) due to the absence of a target site. Here, we show that the zebrafish Junb proteins retain the target site and are phosphorylated by the JNK. Significantly, we found that the phosphorylated Junb proteins (pJunbs) are necessary for adult and larval tissue regeneration, suggesting that the regulation of Junb proteins by phosphorylation is one of the molecular bases for the higher regeneration ability in zebrafish. We also show that the prolonged expression of junbs and their protein phosphorylation by the JNK after the wound healing stage are the unique and necessary features for regeneration. Thus, our data suggest that the transcriptional and post-transcriptional controls of junbs and their protein products are the important regulative steps that enable tissue regeneration in zebrafish.