Casein Kinase I Protein Hrr25 Is Required for Pin4 Phosphorylation and Mediates Cell Wall Integrity Signaling in Saccharomyces cerevisiae

酪蛋白激酶 I 蛋白 Hrr25 是 Pin4 磷酸化所必需的,并介导酿酒酵母中的细胞壁完整性信号传导

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作者:Amita Bhattarai, Manika Bhondeley, Zhengchang Liu

Background

Casein kinase I protein Hrr25 plays important roles in many cellular processes, including autophagy, vesicular trafficking, ribosome biogenesis, mitochondrial biogenesis, and the DNA damage response in Saccharomyces cerevisiae. Pin4 is a multi-phosphorylated protein that has been reported to be involved in the cell wall integrity (CWI) pathway and DNA damage response. Pin4 was reported to interact with Hrr25 in yeast two-hybrid and large-scale pulldown assays.

Conclusions

Our data suggest that Hrr25 is implicated in cell wall integrity signaling via its association with Pin4.

Results

We show that Hrr25 interacts with Pin4 and is required for Pin4 phosphorylation. pin4 mutations result in synthetic slow-growth phenotypes with mutations in genes encoding Bck1 and Slt2, two of the protein kinases in the MAP kinase cascade that regulates CWI in the budding yeast. We show that hrr25 mutations result in similar phenotypes to pin4 mutations. Hrr25 consists of an N-terminal kinase domain, a middle region, and a C-terminal proline/glutamine-rich domain. The function of the C-terminal P/Q-rich domain of Hrr25 has been elusive. We found that the C-terminal region of Hrr25 is required both for Pin4 interaction and CWI. Conclusions: Our data suggest that Hrr25 is implicated in cell wall integrity signaling via its association with Pin4.

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