RNA‐binding protein Csx1 is phosphorylated by LAMMER kinase, Lkh1, in response to oxidative stress in Schizosaccharomyces pombe

Abstract

Recent studies have shown that global gene expression during oxidative stress in Schizosaccharomyces pombe is regulated by stress-induced activation and binding of Csx1 to atf1 + mRNA. However, the kinase responsible for the activation of Csx1 has not been identified. Here, we describe, for the first time, that Csx1 is phosphorylated by S. pombe LAMMER kinase, Lkh1, under oxidative conditions and that the stressactivated binding of the Csx1 to the atf1 + mRNA was also affected by Lkh1 and Spc1. These data indicate that concerted actions of Spc1 and Lkh1 are required for the activation of Csx1 during oxidative condition in the fission yeast S. pombe.

The LAMMER Kinase Homolog, Lkh1, Regulates Tup Transcriptional Repressors through Phosphorylation in Schizosaccharomyces pombe

“…Although a cellular function for LAMMER kinase in fungi has not yet been described, the lkh1 deletion mutant of Schizosaccharomyces pombe reveals various phenotypes, including abnormality in cell division (3, 18); flocculation in liquid medium and filamentous and adhesive growth on agar (3); and sensitivity to oxidative stress (19, 20). Recently, we found that phosphorylation by Lkh1 is required for the activation of Csx1, which protects mRNAs encoding the transcription factor, Atf1, from exonuclease-mediated decay under oxidative conditions (20).…”

“…Recently, we found that phosphorylation by Lkh1 is required for the activation of Csx1, which protects mRNAs encoding the transcription factor, Atf1, from exonuclease-mediated decay under oxidative conditions (20). This suggests that Lkh1 may play important roles in regulating gene expression in S. pombe ; however, the mode of Lkh1 action remains to be determined.…”

Oxidative stress response pathways: Fission yeast as archetype

“…LKs show dual substrate specificity and are capable of autophosphorylation (Howell et al, 1991). In addition to its diverse physiological roles, the single fission yeast LK, namely Lkh1/Kic1 (Kim et al, 2001), phosphorylates Csx1 and, thus, plays an essential role in the stress-induced posttranscriptional regulation of gene expression (Kang et al, 2007). Lkh1-mediated phosphorylation of Csx1 results in increased stability of the atf1 transcript and induction of diverse stress-defense genes, including sod1 and ctt1/cta1 (James et al, 2009;Park et al, 2003).…”

“…Lkh1-mediated phosphorylation of Csx1 results in increased stability of the atf1 transcript and induction of diverse stress-defense genes, including sod1 and ctt1/cta1 (James et al, 2009;Park et al, 2003). The stress-related activity of Lkh1 is presumably regulated through the Sty1 pathway (Figure 4) (Kang et al, 2007).…”

Possible Roles of LAMMER Kinase Lkh1 in Fission Yeast by Comparative Proteome Analysis

“…Recently, the Csx1 protein, which contains three RNA-recognition motifs, has been reported to bind directly to atf1 + mRNA in response to oxidative stress but not other stresses, and also to maintain normal levels of Atf1 by stabilizing atf1 + mRNA under oxidative-stress conditions [3]. Csx1 is phosphorylated by Lkh1 in response to oxidative stress, and the stress-activated binding of Csx1 to atf1 + mRNA is also affected by Lkh1 and Spc1 [4]. …”