Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity

Abstract

In all living organisms, appropriate reactions to unfavorable environmental conditions (stress factors) are observed. When transcription in eukaryotic cells is controlled by extracellular signals, at least one signaling component has to be translocated from the cytoplasm to the nucleus in a signal-dependent manner. The signaling components may be of low molecular weight (second messengers) or protein members of the signaling cascades. Examples for the latter are MAP kinases, for example, the p42 MAP kinase and p44 ERK1 on mitogenic stimulation (Chen et al. 1992).Regulated nuclear translocation is also found widely at the level of transcription factors and is achieved by either cytoplasmic anchoring or activation of nuclear localization signals (NLS) by unmasking or modification (Jans 1995;Gö rlich and Mattaj 1996;Nigg 1997). A prominent example of this type of control is provided by NF-B. A rapid transcriptional response to a variety of stress stimuli is elicited by phosphorylation of the inhibitory factor IB followed by its dissociation from the transcription factor and destruction. This leads to unmasking of the NF-B nuclear localization signal and to the subsequent translocation to the nucleus (Siebenlist, et al. 1995;Baldwin 1996). Another example is NF-ATc, a transcription factor involved in early immune responses that is translocated to the nucleus on dephosphorylation by Ca 2+

Simultaneous yet Independent Regulation of Actin Cytoskeletal Organization and Translation Initiation by Glucose inSaccharomyces cerevisiae

“…In strong support of this hypothesis, a reg1⌬ snf1⌬ double mutant depolarized as rapidly as wild type ( Figure 5, Aa and Ba). These results all parallel those obtained previously with respect to the rapid inhibition of translation initiation upon glucose removal (Ashe et al, 2000).In the cAPK pathway, cAPK negatively regulates the stress-responsive transcription factors Msn2p and Msn4p by inhibiting their nuclear import (Ruis and Schuller, 1995;Gö rner et al, 1998Gö rner et al, , 2002. A tpk1 w mutant (tpk1-1w tpk2⌬ tpk3⌬), which has a low level of cAPK activity, was largely resistant to actin depolarization upon glucose removal, whereas a tpk1⌬ tpk2⌬ tpk3⌬ msn2⌬ msn4⌬ strain depolarized as rapidly as wild type ( Figure 5, Ac and Bb).…”

“…In the cAPK pathway, cAPK negatively regulates the stress-responsive transcription factors Msn2p and Msn4p by inhibiting their nuclear import (Ruis and Schuller, 1995;Gö rner et al, 1998Gö rner et al, , 2002. A tpk1 w mutant (tpk1-1w tpk2⌬ tpk3⌬), which has a low level of cAPK activity, was largely resistant to actin depolarization upon glucose removal, whereas a tpk1⌬ tpk2⌬ tpk3⌬ msn2⌬ msn4⌬ strain depolarized as rapidly as wild type ( Figure 5, Ac and Bb).…”

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

“…Upon glucose exhaustion, they are hyperphosphorylated and translocated to the nucleus, where they induce expression of the STREcontrolled genes. PKA inhibits nuclear import of Msn2/4, probably through direct phosphorylation of their nuclear localization signal (Gorner et al 1998(Gorner et al , 2002Garreau et al 2000). A second mechanism for PKA-mediated regulation of STRE-controlled gene expression involves the Ccr4-Not complex, a global transcriptional regulator that affects genes positively and negatively.…”

“…On the other hand, TORC1 inhibits the transcription of stress-responsive genes via a Rim15-independent, but Tap42-PP2A-dependent route, thereby promoting the phosphorylation and cytoplasmic retention of Msn2 (Beck and Hall 1999; Duvel et al 2003;Santhanam et al 2004). It is important to note that the latter is independent of the PKA-mediated phosphorylation of the Msn2/4 nuclear localization signal (Gorner et al 1998(Gorner et al , 2002Garreau et al 2000;Santhanam et al 2004).…”

Stress‐activated signalling pathways in yeast

“…Consequently, S. cerevisiae strains with low PKA activity are more stress resistant than mutants exhibiting high PKA activity (Shin et al 1987). Recent experiments performed by Gorner et al (1998) suggest a mechanism for how PKA may be affecting STREdependent regulation. They found that Msn2 and Msn4 are localized to the cytoplasm of unstressed cells, and that both proteins quickly accumulate in the nucleus following imposition of stress (Fig.…”