On how a transcription factor can avoid its proteolytic activation in the absence of signal transduction

Espeso, Eduardo A.; Roncal, Tomàs; Díez, Eliecer; Rainbow, Lynne; Bignell, Elaine; Álvaro, Josué; Suárez, Teresa; Denison, Steven H.; Tilburn, Joan; Arst, Herbert N.; Peñalva, Miguel

doi:10.1038/sj.emboj.7593063b

Cited by 7 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the alkalinity mimicry of pacC c/− 20000 (5‐251 + 5) is enhanced, with respect to morphology, by pacX − , but pacC c/− 20601 (5‐260) (Mingot et al ., ), which contains the intact processed form and has a similar phenotype, appears to be unaffected. pacC c 69 (L340S) and pacC c 50 (5‐266) (Tilburn et al ., ; Mingot et al ., ; Espeso et al ., ) do not appear to be phenotypically enhanced by pacX 1, possibly because increased alkalinity mimicry in these strong constitutive backgrounds requires sensitivity beyond that of Petri dish tests. Lack of suppression of acidity mimicking mutants pacC +/− 230 (PacC5‐238fs) and pacC +/− 206 (PacC5‐310fs) (Mingot et al ., ), which are both suppressed by mutations affecting the proteasomal degradative pathway (JT and HNA, unpublished), suggests that the effects of pacX 1 are insufficient to offset this process.…”

Section: Resultsmentioning

confidence: 98%

“…On shifting to alkalinity, levels of PacC 72 remain fairly constant in both palB 38 strains and appreciable amounts of PacC 27 and partial degradation products in the palB 38 pacX 20 strain are detectable throughout. These bands are attributable to C‐terminal, processive, Pal‐independent proteolysis of the minor proportion of PacC 72 having an ‘open’, and proteasome accessible, conformation that exists in equilibrium with the much more numerous PacC 72 molecules that are ‘closed’ and proteasome resistant (Espeso and Arst, ; Espeso et al ., ; Díez et al ., ; Hervás‐Aguilar et al ., ; Peñas et al ., ; Peñalva et al ., ).…”

Section: Resultsmentioning

confidence: 99%

“…The pH response is mediated by the three Cys2‐His2 finger transcription factor, A. nidulans PacC (Tilburn et al ., ) or Rim101 in S. cerevisiae (Su and Mitchell, ). Under acidic conditions, the A. nidulans PacC full‐length form, PacC 72 , is protease inaccessible due to intramolecular‐interactions involving the C‐terminal moiety (Espeso et al ., ). At neutral to alkaline ambient pH PacC undergoes two‐step proteolysis.…”

Section: Introductionmentioning

confidence: 97%

“…pacC mutations that remove the PacC 72 C‐terminus or otherwise disrupt its intramolecular‐interactions result in an open, proteasome‐accessible conformation leading to constitutive PacC processing and alkalinity mimicry (Orejas et al ., ; Tilburn et al ., ; Espeso et al ., ). Loss‐of‐function mutations in the pal (pH signal transduction) genes or pacC result in acidity mimicry (Arst et al ., ; Tilburn et al ., ; Fernández‐Martínez et al ., ).…”

Section: Introductionmentioning

confidence: 97%

See 3 more Smart Citations

Refining the pH response in Aspergillus nidulans: a modulatory triad involving PacX, a novel zinc binuclear cluster protein

Bussink

Bignell

Múnera-Huertas

et al. 2015

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

SummaryThe A spergillus nidulans PacC transcription factor mediates gene regulation in response to alkaline ambient pH which, signalled by the Pal pathway, results in the processing of PacC72 to PacC27 via PacC53. Here we investigate two levels at which the pH regulatory system is transcriptionally moderated by pH and identify and characterise a new component of the pH regulatory machinery, PacX. Transcript level analysis and overexpression studies demonstrate that repression of acid‐expressed pal F, specifying the Pal pathway arrestin, probably by PacC27 and/or PacC53, prevents an escalating alkaline pH response. Transcript analyses using a reporter and constitutively expressed pac C trans‐alleles show that pac C preferential alkaline‐expression results from derepression by depletion of the acid‐prevalent PacC72 form. We additionally show that pac C repression requires PacX. pac X mutations suppress PacC processing recalcitrant mutations, in part, through derepressed PacC levels resulting in traces of PacC27 formed by pH‐independent proteolysis. pac X was cloned by impala transposon mutagenesis. PacX, with homologues within the Leotiomyceta, has an unusual structure with an amino‐terminal coiled‐coil and a carboxy‐terminal zinc binuclear cluster. pacX mutations indicate the importance of these regions. One mutation, an unprecedented finding in A . nidulans genetics, resulted from an insertion of an endogenous Fot1‐like transposon.

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Refining the pH response in Aspergillus nidulans: a modulatory triad involving PacX, a novel zinc binuclear cluster protein

Bussink

Bignell

Múnera-Huertas

et al. 2015

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…pacC c 69 leads to PacC processing at any ambient pH. Its Leu340Ser substitution within interactive region B (Espeso et al ., 2000) disrupts the ‘closed’ PacC conformation. As in the wild‐type, shifting cells to alkaline conditions rapidly leads to the formation of the intermediate at the expense of the full‐length form (Figure 7C), showing that the mutation does not affect the signalling protease step.…”

Section: Resultsmentioning

confidence: 99%

Activation of theAspergillusPacC zinc finger transcription factor requires two proteolytic steps

et al. 2002

Self Cite

View full text Add to dashboard Cite

The Aspergillus PacC transcription factor undergoes proteolytic activation in response to alkaline ambient pH. In acidic environments, the 674 residue translation product adopts a ‘closed’ conformation, protected from activation through intramolecular interactions involving the ≤150 residue C‐terminal domain. pH signalling converts PacC to an accessible conformation enabling processing cleavage within residues 252–254. We demonstrate that activation of PacC requires two sequential proteolytic steps. First, the ‘closed’ translation product is converted to an accessible, committed intermediate by proteolytic elimination of the C‐terminus. This ambient pH‐regulated cleavage is required for the final, pH‐independent processing reaction and is mediated by a distinct signalling protease (possibly PalB). The signalling protease cleaves PacC between residues 493 and 500, within a conserved 24 residue ‘signalling protease box’. Precise deletion or Leu498Ser substitution prevents formation of the committed and processed forms, demonstrating that signalling cleavage is essential for final processing. In contrast, signalling cleavage is not required for processing of the Leu340Ser protein, which lacks interactions preventing processing. In its two‐step mechanism, PacC processing can be compared with regulated intramembrane proteolysis.

show abstract

The pH signalling transcription factor PacC controls virulence in the plant pathogen Fusarium oxysporum

Caracuel¹,

Roncero²,

Espeso³

et al. 2003

Molecular Microbiology

Self Cite

194

199

View full text Add to dashboard Cite

SummaryGene expression in fungi by ambient pH is regulated via a conserved signalling cascade whose terminal component is the zinc finger transcription factor PacC/Rim1p. We have identified a pacC orthologue in the vascular wilt pathogen Fusarium oxysporum that binds the consensus 5 ¢ ¢ ¢ ¢ -GCCAAG-3 ¢ ¢ ¢ ¢ sequence and is proteolytically processed in a similar way to PacC from Aspergillus nidulans. pacC transcript levels were elevated in F. oxysporum grown in alkaline conditions and almost undetectable at extreme acidic growth conditions. PacC + + + + /-loss-of-function mutants displayed an acidity-mimicking phenotype resulting in poor growth at alkaline pH, increased acid protease activity and higher transcript levels of acid-expressed polygalacturonase genes. Reintroduction of a functional pacC copy into a pacC + + + + /-mutant restored the wild-type phenotype. Conversely, F. oxysporum merodiploids carrying a dominant activating pacC c allele had increased pacC transcript and protein levels and displayed an alkalinity-mimicking phenotype with reduced acid phosphatase and increased alkaline protease activities. PacC + + + + /-mutants were more virulent than the wild-type strain in root infection assays with tomato plants, whereas pacC c strains were significantly reduced in virulence. We propose that F. oxysporum PacC acts as a negative regulator of virulence to plants, possibly by preventing transcription of acid-expressed genes important for infection.

show abstract

On how a transcription factor can avoid its proteolytic activation in the absence of signal transduction

Cited by 7 publications

References 0 publications

Refining the pH response in Aspergillus nidulans: a modulatory triad involving PacX, a novel zinc binuclear cluster protein

Refining the pH response in Aspergillus nidulans: a modulatory triad involving PacX, a novel zinc binuclear cluster protein

Activation of theAspergillusPacC zinc finger transcription factor requires two proteolytic steps

The pH signalling transcription factor PacC controls virulence in the plant pathogen Fusarium oxysporum

Contact Info

Product

Resources

About