Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Mol. Cell. Biol. 21 (5): 1688-1699

Copyright © 2001 by the American Society for Microbiology. All rights reserved.

Molecular and Cellular Biology, March 2001, p. 1688-1699, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1688-1699.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Ambient pH Signaling Regulates Nuclear Localization of the Aspergillus nidulans PacC Transcription Factor

José M. Mingot,dagger Eduardo A. Espeso, Eliecer Díez, and Miguel Á. Peñalva*

Centro de Investigaciones Biológicas CSIC, Madrid 28006, Spain

Received 10 August 2000/Returned for modification 11 October 2000/Accepted 7 December 2000

The Aspergillus nidulans zinc finger transcription factor PacC is activated by proteolytic processing in response to ambient alkaline pH. The pH-regulated step is the transition of full-length PacC from a closed to an open, protease-accessible conformation. Here we show that in the absence of ambient pH signaling, the C-terminal negative-acting domain prevents the nuclear localization of full-length closed PacC. In contrast, the processed PacC form is almost exclusively nuclear at any ambient pH. In the presence of ambient pH signaling, the fraction of PacC that is in the open conformation but has not yet been processed localizes to the nucleus. Therefore, ambient alkaline pH leads to an increase in nuclear PacC by promoting the proteolytic elimination of the negative-acting domain to yield the processed form and by increasing the proportion of full-length protein that is in the open conformation. These findings explain why mutations resulting in commitment of PacC to processing irrespective of ambient pH lead to permanent PacC activation and alkalinity mimicry. A nuclear import signal that targets Escherichia coli beta -galactosidase to the nucleus has been located to the PacC zinc finger region. A mutation abolishing DNA binding does not prevent nuclear localization of the processed form, showing that PacC processing does not lead to nuclear localization by passive diffusion of the protein made possible by the reduction in size, followed by retention in the nucleus after DNA binding.

* Corresponding author. Mailing address: Centro de Investigaciones Biológicas CSIC, Velázquez 144, Madrid 28006, Spain. Phone: 34 91 5644562, ext. 4358. Fax: 34 91 5627518. E-mail: penalva{at}

dagger Present address: Zentrum für Molekulare Biologie der Universität Heidelberg, 69120 Heidelberg, Germany.

Molecular and Cellular Biology, March 2001, p. 1688-1699, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1688-1699.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA.
C. C. Hunter, K. S. Siebert, D. J. Downes, K. H. Wong, S. D. Kreutzberger, J. A. Fraser, D. F. Clarke, M. J. Hynes, M. A. Davis, and R. B. Todd (2014)
Eukaryot. Cell 13, 527-538
   Abstract »    Full Text »    PDF »
The Cryptococcus neoformans Rim101 Transcription Factor Directly Regulates Genes Required for Adaptation to the Host.
T. R. O'Meara, W. Xu, K. M. Selvig, M. J. O'Meara, A. P. Mitchell, and J. A. Alspaugh (2014)
Mol. Cell. Biol. 34, 673-684
   Abstract »    Full Text »    PDF »
Expression and promoter characterization of BbPacC, a pH response transcription factor gene of the entomopathogenic fungus Beauveria bassiana.
Y.-H. Zhou, L. Hou, Y.-J. Zhang, Y.-H. Fan, Z.-B. Luo, D. Jin, Q.-S. Zhou, Y.-J. Li, Y. Wang, and Y. Pei (2014)
Microbiology 160, 353-361
   Abstract »    Full Text »    PDF »
The Cryptococcus neoformans Capsule: a Sword and a Shield.
T. R. O'Meara and J. A. Alspaugh (2012)
Clin. Microbiol. Rev. 25, 387-408
   Abstract »    Full Text »    PDF »
Pho85 Kinase, a Cyclin-Dependent Kinase, Regulates Nuclear Accumulation of the Rim101 Transcription Factor in the Stress Response of Saccharomyces cerevisiae.
M. Nishizawa, M. Tanigawa, M. Hayashi, T. Maeda, Y. Yazaki, Y. Saeki, and A. Toh-e (2010)
Eukaryot. Cell 9, 943-951
   Abstract »    Full Text »    PDF »
Organization and Dynamics of the Aspergillus nidulans Golgi during Apical Extension and Mitosis.
A. Pantazopoulou and M. A. Penalva (2009)
Mol. Biol. Cell 20, 4335-4347
   Abstract »    Full Text »    PDF »
Establishment of the Ambient pH Signaling Complex in Aspergillus nidulans: PalI Assists Plasma Membrane Localization of PalH.
A. M. Calcagno-Pizarelli, S. Negrete-Urtasun, S. H. Denison, J. D. Rudnicka, H.-J. Bussink, T. Munera-Huertas, L. Stanton, A. Hervas-Aguilar, E. A. Espeso, J. Tilburn, et al. (2007)
Eukaryot. Cell 6, 2365-2375
   Abstract »    Full Text »    PDF »
Evidence for Novel pH-Dependent Regulation of Candida albicans Rim101, a Direct Transcriptional Repressor of the Cell Wall {beta}-Glycosidase Phr2.
Y.-U. Baek, S. J. Martin, and D. A. Davis (2006)
Eukaryot. Cell 5, 1550-1559
   Abstract »    Full Text »    PDF »
Diverged Binding Specificity of Rim101p, the Candida albicans Ortholog of PacC.
A. M. Ramon and W. A. Fonzi (2003)
Eukaryot. Cell 2, 718-728
   Abstract »    Full Text »    PDF »
YPXL/I Is a Protein Interaction Motif Recognized by Aspergillus PalA and Its Human Homologue, AIP1/Alix.
O. Vincent, L. Rainbow, J. Tilburn, H. N. Arst Jr., and M. A. Penalva (2003)
Mol. Cell. Biol. 23, 1647-1655
   Abstract »    Full Text »    PDF »
The Transcription Factor Rim101p Governs Ion Tolerance and Cell Differentiation by Direct Repression of the Regulatory Genes NRG1 and SMP1 in Saccharomyces cerevisiae.
T. M. Lamb and A. P. Mitchell (2003)
Mol. Cell. Biol. 23, 677-686
   Abstract »    Full Text »    PDF »
Regulation of Gene Expression by Ambient pH in Filamentous Fungi and Yeasts.
M. A. Penalva and H. N. Arst Jr. (2002)
Microbiol. Mol. Biol. Rev. 66, 426-446
   Abstract »    Full Text »    PDF »
Activation of the Aspergillus PacC zinc finger transcription factor requires two proteolytic steps.
E. Diez, J. Alvaro, E. A. Espeso, L. Rainbow, T. Suarez, J. Tilburn, H. N. Arst Jr, and M. A. Penalva (2002)
EMBO J. 21, 1350-1359
   Abstract »    Full Text »    PDF »
Genetic Control of Extracellular Protease Synthesis in the Yeast Yarrowia lipolytica.
C. I. Gonzalez-Lopez, R. Szabo, S. Blanchin-Roland, and C. Gaillardin (2002)
Genetics 160, 417-427
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882