The protein kinase C‐mediated MAP kinase pathway involved in the maintenance of cellular integrity in <i>Saccharomyces cerevisiae</i>

Heinisch, Jürgen J.; Lorberg, Anja; Schmitz, Hans‐Peter; Jacoby, Jörg J.

doi:10.1046/j.1365-2958.1999.01375.x

Cited by 311 publications

(284 citation statements)

References 66 publications

Supporting

Mentioning

279

Contrasting

Unclassified

Order By: Relevance

“…Activation of the CI pathway, which responds to weakening or stretching of the cell wall and functions to activate the synthesis and delivery of cell wall components (Gustin et al, 1998;Heinisch et al, 1999), increases both the rate of ER stress-mediated induction of HAC1 mRNA splicing (Helfenbaum, unpublished data) and the stability of Hac1p, suggesting that the multicopy suppression occurred because the increased level of accumulation of Hac1p compensated for its reduced affinity for the point mutated UPRE element. Analysis of the roles played by the CI pathway kinases indicated that Pkc1p was necessary for acceleration of HAC1 mRNA splicing under hypotonic shock conditions that activate CI signaling (Helfenbaum, unpublished data), whereas both Pkc1p and Mpk1p were required for stabilization of Hac1p even under normal (isotonic) conditions.…”

Section: Discussionmentioning

confidence: 99%

“…In a separate study we recently showed that overexpression of components of the cell integrity (CI) MAP kinase signal transduction pathway, which regulates cell integrity by upregulating cell wall synthesis in response to weakening or stretching of the cell wall (Gustin et al, 1998;Heinisch et al, 1999), suppresses the transcriptional defect of a reporter gene controlled by a point mutated UPRE element (Helfenbaum, unpublished data). This raised the possibility of a previously unrecognized interaction between the UPR and CI responses.…”

Section: Activation Of the Cell Integrity Map Kinase Pathway Stabilizmentioning

confidence: 99%

See 1 more Smart Citation

SCF^Cdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

Pal

Chan

Helfenbaum

et al. 2007

MBoC

View full text Add to dashboard Cite

The Saccharomyces cerevisiae basic leucine zipper transcription factor Hac1p is synthesized in response to the accumulation of unfolded polypeptides in the lumen of the endoplasmic reticulum (ER), and it is responsible for up-regulation of ϳ5% of all yeast genes, including ER-resident chaperones and protein-folding catalysts. Hac1p is one of the most short-lived yeast proteins, having a half-life of ϳ1.5 min. Here, we have shown that Hac1p harbors a functional PEST degron and that degradation of Hac1p by the proteasome involves the E2 ubiquitin-conjugating enzyme Ubc3/Cdc34p and the SCF Cdc4 E3 complex. Consistent with the known nuclear localization of Cdc4p, rapid degradation of Hac1p requires the presence of a functional nuclear localization sequence, which we demonstrated to involve basic residues in the sequence 29 RKRAKTK 35 . Two-hybrid analysis demonstrated that the PEST-dependent interaction of Hac1p with Cdc4p requires Ser146 and Ser149. Turnover of Hac1p may be dependent on transcription because it is inhibited in cell mutants lacking Srb10 kinase, a component of the SRB/mediator module of the RNA polymerase II holoenzyme. Stabilization of Hac1p by point mutation or deletion, or as the consequence of defects in components of the degradation pathway, results in increased unfolded protein response element-dependent transcription and improved cell viability under ER stress conditions. INTRODUCTIONIn eukaryotic cells, the endoplasmic reticulum (ER) is the portal for newly synthesized proteins destined for all compartments of the exocytic and endocytic pathways as well as for the cell surface and the extracellular space. Transport along the exocytic pathway requires that passenger proteins are correctly folded and assembled (Gething et al., 1986; for review, see Ellgaard and Helenius, 2003), a process that is assisted by molecular chaperones and folding catalysts resident in the ER lumen (for review, see van Anken and Braakman, 2005). The concentrations of these components in the ER are adjusted according to need by the unfolded protein response (UPR; Kozutsumi et al., 1988;Mori et al., 1992; for review, see Kaufman, 1999;Ma and Hendershot, 2001;Patil and Walter, 2001;Schrö der and Kaufman, 2005). The UPR regulates the transcription of ϳ5% of the open reading frames in the Saccharomyces cerevisiae genome, many of which encode proteins with functions involved in diverse processes, including protein translocation, glycosylation, folding and degradation, lipid/inositol metabolism, vesicular trafficking, vacuolar protein sorting, and cell wall biogenesis (Travers et al., 2000).The yeast unfolded protein response (UPR) involves two unique participants, the Ire1p transmembrane receptor kinase/endonuclease (Cox et al., 1993;Mori et al., 1993), and the basic leucine zipper (bZip) transcription factor Hac1p Mori et al., 1996), which transactivates genes bearing UPRE elements (Mori et al., 1992(Mori et al., , 1998Patil and Walter, 2004). HAC1 mRNA is synthesized constitutively as a precursor bearing a 252-nucleotid...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Activation Of the Cell Integrity Map Kinase Pathway Stabilizmentioning

confidence: 99%

SCF^Cdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

Pal

Chan

Helfenbaum

et al. 2007

MBoC

View full text Add to dashboard Cite

show abstract

“…In general, such stresses are detected at the cell surface and further transduced by a specific signalling cascade, which ultimately directs new wall synthesis (reviewed in Heinisch et al, 1999;Levin, 2005). This signalling includes a set of plasma membrane sensors comprised by the Wsc protein family (Slg1/Wsc1, Wsc2, Wsc3; Verna et al, 1997), the Mid2 sensor and its homologue Mtl1 (Ketela et al, 1999;Rajavel et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The effect of tea tree oil and antifungal agents on a reporter for yeast cell integrity signalling

Straede

Corran

Bundy

et al. 2007

Yeast

View full text Add to dashboard Cite

Cell integrity in Saccharomyces cerevisiae is ensured by a rigid cell wall whose synthesis is controlled by a highly conserved MAP kinase signal transduction cascade. Stress at the cell surface is detected by a set of sensors and ultimately transmitted through this cascade to the transcription factor Rlm1, which governs expression of many genes encoding enzymes of cell wall biosynthesis. We here report on a number of versatile reporter constructs which link activation of a hybrid, Rlm1-lexA, by the MAP kinase Mpk1/Slt2 to the expression of the bacterial lacZ gene. This system was adapted to automated microwell screening and shown to be activated by a number of compounds inhibiting cell wall biosynthesis or interfering with plasma membrane function. In addition, we tested tea tree oil and two of its purified constituents (α-terpineol, terpinen-4-ol) for their effects on growth and on cell integrity signalling using such reporter strains. Tea tree oil was found to inhibit growth of wild-type and slg1/wsc1 mutant cells at a threshold of approximately 0.1% v/v, with the purified compounds acting already at half these concentrations. A mid2 deletion displayed hyper-resistance. Tea tree oil also induces the signalling pathway in a dose-dependent manner.

show abstract

“…On the other hand, cell cycle arrest and repolarization of cell growth in the form of a mating projection, or "shmoo," toward the source of the mating signal leads to remodeling of the cell wall, a process that is dependent upon the cell integrity cascade (Buehrer and Errede, 1997;Roberts et al, 2000). The cell integrity pathway regulates cell wall and actin cytoskeleton dynamics (Schmidt and Hall, 1998;Heinisch et al, 1999). It is under the control of protein kinase and is comprised of Bck1 (an MAPKKK), Mkk1 and Mkk2 (an MAPKK), and Mpk1 (an MAPK).…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Staleva

Hall

Orlow

2004

MBoC

View full text Add to dashboard Cite

Mating in haploid Saccharomyces cerevisiae occurs after activation of the pheromone response pathway. Biochemical components of this pathway are involved in other yeast signal transduction networks. To understand more about the coordination between signaling pathways, we used a "chemical genetic" approach, searching for compounds that would activate the pheromone-responsive gene FUS1 and RLM1, a reporter for the cell integrity pathway. We found that catecholamines (L-3,4-hydroxyphenylalanine [L-dopa], dopamine, adrenaline, and noradrenaline) elevate FUS1 and RLM1 transcription. N-Acetyl-cysteine, a powerful antioxidant in yeast, completely reversed this effect, suggesting that FUS1 and RLM1 activation in response to catecholamines is a result of oxidative stress. The oxidant hydrogen peroxide also was found to activate transcription of an RLM1 reporter. Further genetic analysis combined with immunoblotting revealed that Kss1, one of the mating mitogen-activated protein kinases (MAPKs), and Mpk1, an MAPK of the cell integrity pathway, participated in L-dopa-induced stimulation of FUS1 and RLM1 transcription. We also report that Mpk1 and Hog1, the high osmolarity MAPK, were phosphorylated upon induction by hydrogen peroxide. Together, our results demonstrate that cells respond to oxidative stress via different signal transduction machinery dependent upon the nature of the oxidant. INTRODUCTIONIn the haploid cells of the yeast Saccharomyces cerevisiae, four essential MAPK cascades (Figure 1) respond to different external signals to mediate specific responses. The mating pathway is activated by peptide pheromones and induces cell-cycle arrest and the morphological changes required for mating (Elion, 1998;Gustin et al., 1998). The invasive growth pathway is activated by starvation and induces foraging into the agar substratum. The high osmolarity glycerol (HOG) pathway increases intracellular glycerol levels in response to hypertonic stress, whereas the cell integrity pathway is activated by hypotonic stress, heat shock, or impaired cell wall synthesis. Recently, an additional MAPK cascade has been described: the Kss1 vegetative growth pathway (Lee and Elion, 1999). The Kss1 pathway may be activated by cell wall stress or changes in osmolarity (Cullen et al., 2000).The mating pathway is the most studied cellular response to an external signal. As a relatively simple G protein-coupled cascade, it is a widely used model to study mammalian G protein-coupled receptors. The mating cascade includes pheromone receptors (Ste2 and Ste3), G proteins (Gpa1, Ste4, and Ste18), the p21 activating protein kinase Ste20, a mitogen-activated protein kinase kinase kinase (MAPKKK) Ste11, a mitogen-activated protein kinase kinase (MAPKK) Ste7, a scaffolding protein Ste5 and two MAPKs (Fus3 and Kss1) (Gustin et al., 1998;Madhani and Fink, 1998;Farley et al., 1999). Targets of the terminal MAPK include Ste12, a factor required for transcription of pheromone-responsive genes, and Far1, a bifunctional protein required for polarization and G1...

show abstract

The protein kinase C‐mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae

Cited by 311 publications

References 66 publications

SCF^Cdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

SCF^Cdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

The effect of tea tree oil and antifungal agents on a reporter for yeast cell integrity signalling

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Contact Info

Product

Resources

About

The protein kinase C‐mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae

Cited by 311 publications

References 66 publications

SCFCdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

SCFCdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

The effect of tea tree oil and antifungal agents on a reporter for yeast cell integrity signalling

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Contact Info

Product

Resources

About

SCF^Cdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

SCF^Cdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae