NHP6A and NHP6B, which encode HMG1-like proteins, are candidates for downstream components of the yeast SLT2 mitogen-activated protein kinase pathway

Christine Costigan, David Kolodrubetz, Michael Snyder

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

The yeast SLK1 (BCK1) gene encodes a mitogen-activated protein kinase (MAPK) activator protein which functions upstream in a protein kinase cascade that converges on the MAPK Slt2p (Mpk1p). Dominant alleles of SLK1 have been shown to bypass the conditional lethality of a protein kinase C mutation, pkc1-Δ, suggesting that Pkc1p may regulate Slk1p function. Slk1p has an important role in morphogenesis and growth control, and deletions of the SLK1 gene are lethal in a spa2-Δ mutant background. To search for genes that interact with the SLK1-SLT2 pathway, a synthetic lethal suppression screen was carried out. Genes which in multiple copies suppress the synthetic lethality of slk1-1 spa2-Δ were identified, and one, the NHP6A gene, has been extensively characterized. The NHP6A gene and the closely related NHP6B gene were shown previously to encode HMG1-like chromatin-associated proteins. We demonstrate here that these genes are functionally redundant and that multiple copies of either NHP6A or NHP6B suppress slk1-Δ and slt2-Δ. Strains from which both NHP6 genes were deleted (nhp6-Δ mutants) share many phenotypes with pkc1-Δ, slk1-Δ, and slt2-Δ mutants. nhp6-Δ cells display a temperature-sensitive growth defect that is rescued by the addition of 1 M sorbitol to the medium, and they are sensitive to starvation. nhp6-Δ strains also exhibit a variety of morphological and cytoskeletal defects. At the restrictive temperature for growth, nhp6-Δ mutant cells contain elongated buds and enlarged necks. Many cells have patches of chitin staining on their cell surfaces, and chitin deposition is enhanced at the necks of budded cells. nhp6-Δ cells display a defect in actin polarity and often accumulate large actin chunks. Genetic and phenotypic analysis indicates that NHP6A and NHP6B function downstream of SLT2. Our results indicate that the Slt2p MAPK pathway in Saccharomyces cerevisiae may mediate its function in cell growth and morphogenesis, at least in part, through high-mobility group proteins.

Original languageEnglish (US)
Pages (from-to)2391-2403
Number of pages13
JournalMolecular and cellular biology
Volume14
Issue number4
DOIs
StatePublished - Apr 1994

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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