Abstract
Ankyrin repeats, the most common protein–protein interaction motifs in nature, are widely present in proteins of both eukaryotic and prokaryotic cells. Ankyrin repeat-containing proteins play diverse biological functions. Here, we identified the gene ankrd45, which encodes a novel, two ankyrin repeat-containing protein. Zebrafish ankrd45 displayed a tissue specific expression pattern during early development, with high expression in ciliated tissues, including otic vesicles, Kupffer’s vesicles, pronephric ducts, and floor plates. Surprisingly, zebrafish ankrd45 mutants were viable and developed grossly normal cilia. In contrast, mutant larvae developed enlarged livers when induced with liver specific expression of KrasG12V, one of the common mutations of KRAS that leads to cancer in humans. Further, histological analysis suggested that multiple cysts developed in the mutant liver due to cell apoptosis. Similarly, knockdown of ANKRD45 expression with either siRNA or CRISPR/Cas9 methods induced apoptosis in cultured cells, similar to those in zebrafish ankrd45 mutant livers after induction. Using different cell lines, we show that the distribution of ANKRD45 protein was highly dynamic during mitosis. ANKRD45 is preferably localized to the midbody ring during cytokinesis. Together, our results suggest that ANKRD45 is a novel ankyrin repeat protein with a conserved role during cell proliferation in both zebrafish embryos and mammalian cells.
Highlights
The ankyrin repeat (ANK), a motif of 33 amino acid residues, is one of the most common protein motifs that is widely present in all forms of life, including bacteria, archaea, eukaryotes, and viruses
Considering that many ANK proteins play a role during cell cycle regulation, we investigated whether loss of function of Ankrd45 could lead to cell proliferation defects in zebrafish larvae
Ankyrin repeat-containing proteins are one of the most common protein families present in eukaryotic cells and they play a role in various biological functions
Summary
The ankyrin repeat (ANK), a motif of 33 amino acid residues, is one of the most common protein motifs that is widely present in all forms of life, including bacteria, archaea, eukaryotes, and viruses. ANK repeats were first identified in the yeast cell cycle regulator Swi6/Cdc and the Drosophila cell signaling Notch protein, and later named after the human membrane-associated ankyrin protein, which contains 24 such repeats and regulates the interaction between the cytoskeleton and the plasma membrane [3,4]. Thousands of ANK-containing proteins have been identified, which perform a wide range of functions, including signal transduction, cell cycle regulation, vesicle trafficking, cytoskeletal organization, and transcriptional regulation [2,5]. Mutation of p16, a tumor suppressor protein with four ankyrin repeats, Genes 2019, 10, 462; doi:10.3390/genes10060462 www.mdpi.com/journal/genes
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