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Molecular and Cellular Biology, March 2003, p. 1647-1655, Vol. 23, No. 5
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.5.1647-1655.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

YPXL/I Is a Protein Interaction Motif Recognized by Aspergillus PalA and Its Human Homologue, AIP1/Alix

Olivier Vincent,1* Lynne Rainbow,2,{dagger} Joan Tilburn,2 Herbert N. Arst, Jr.,2 and Miguel A. Peñalva1

Departamento de Microbiología Molecular, Centro de Investigaciones Biológicas del CSIC, Madrid 28006, Spain,1 Department of Infectious Diseases, Faculty of Medicine, Imperial College of Science, Technology & Medicine, London W12 0NN, United Kingdom2

Received 4 October 2002/ Returned for modification 21 November 2002/ Accepted 2 December 2002

The zinc finger transcription factor PacC undergoes two-step proteolytic activation in response to alkaline ambient pH. PalA is a component of the fungal ambient pH signal transduction pathway. Its mammalian homologue AIP1/Alix interacts with the apoptosis-linked protein ALG-2. We show that both PalA and AIP1/Alix recognize a protein-protein binding motif that we denote YPXL/I, where Tyr, Pro, and Leu/Ile are crucial for its interactive properties. Two such motifs flanking the signaling protease cleavage site mediate direct binding of PalA to PacC, required for the first and only pH-regulated cleavage of this transcription factor. PalA can bind the "closed" (i.e., wild-type full-length) conformer of PacC, suggesting that PalA binding constitutes the first stage in the two-step proteolytic cascade, recruiting or facilitating access of the signaling protease, presumably PalB. In addition to recognizing YPXL/I motifs, both PalA and AIP1/Alix interact with the Aspergillus class E Vps protein Vps32 homologue, a member of a protein complex involved in the early steps of the multivesicular body pathway, suggesting that this interaction is an additional feature of proteins of the PalA/AIP1/Alix family.


* Corresponding author. Mailing address: Departamento de Microbiologia Molecular, Centro de Investigaciones Biológicas del CSIC, Velázquez 144, Madrid 28006, Spain. Phone: 34 91 5644562 ext. 4357. Fax: 34 91 5627518. E-mail: ovincent{at}cib.csic.es.

{dagger} Present address: Division of Reproductive and Child Health, Medical and Molecular Genetics, The Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom.


Molecular and Cellular Biology, March 2003, p. 1647-1655, Vol. 23, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.5.1647-1655.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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