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

Abstract

Disruption of the fission yeast LAMMER kinase, Lkh1, gene resulted in diverse phenotypes, including adhesive filamentous growth and oxidative stress sensitivity, but an exact cellular function had not been assigned to Lkh1. Through an in vitro pull-down approach, a transcriptional repressor, Tup12, was identified as an Lkh1 binding partner. Interactions between Lkh1 and Tup11 or Tup12 were confirmed by in vitro and in vivo binding assays. Tup proteins were phosphorylated by Lkh1 in a LAMMER motif-dependent manner. The LAMMER motif was also necessary for substrate recognition in vitro and cellular function in vivo. Transcriptional activity assays using promoters negatively regulated by Tup11 and Tup12 showed 6 or 2 times higher activity in the Δlkh1 mutant than the wild type, respectively. Northern analysis revealed derepressed expression of the fbp1+ mRNA in Δlkh1 and in Δtup11Δtup12 mutant cells under repressed conditions. Δlkh1 and Δtup11Δtup12 mutant cells showed flocculation, which was reversed by co-expression of Tup11 and -12 with Ssn6. Here, we presented a new aspect of the LAMMER kinase by demonstrating that the activities of global transcriptional repressors, Tup11 and Tup12, were positively regulated by Lkh1-mediated phosphorylation.

MADS Box Transcription Factor Mbx2/Pvg4 Regulates Invasive Growth and Flocculation by Inducing gsf2 + Expression in Fission Yeast

“…The fission yeast LAMMER kinase homolog, Lkh1, regulates Tup transcriptional repressors through phosphorylation, and an lkh1 null mutant flocculates upon reaching stationary phase in liquid media and adheres to agar surfaces (15). In addition, we previously isolated a fission yeast gsf1 mutant that flocculates constitutively during growth in liquid media and also adheres to agar (20,37).…”

Reduction of Ribosome Level Triggers Flocculation of Fission Yeast Cells

“…Lkh1 encodes a LAMMER kinase homolog, which represses expression of adhesions (12). Kang et al (2010) also showed that deletion of the tup12 ϩ gene, functioning as a Lkh1 binding partner, resulted in a nonsexual flocculation in the fission yeast (13). Recently, Matsuzawa et al (2011) reported that overexpression of FLO8, encoding a transcriptional activator of the dominant flocculation genes in budding yeast Saccharomyces cerevisiae, induced a nonsexual flocculation in fission yeast (14).…”

Diverse roles of Groucho/Tup1 co-repressors in plant growth and development

“…It is also possible that co-repressor activity can be altered through post-translational modifications such as phosphorylation and sumoylation. While these modifications affect the binding properties of Gro/Tup1 proteins in animals and fungi, [61][62][63][64] it is presently not clear whether such mechanisms are also used to control plant co-repressor activity.…”