The PTF1 (pancreas transcription factor 1) complex is a master regulator of differentiation of acinar cells, responsible for the production of digestive enzymes. In the adult pancreas, PTF1 contains two pancreas-restricted transcription factors: Ptf1a and Rbpjl. PTF1 recruits P/CAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] which acetylates Ptf1a and enhances its transcriptional activity. Using yeast two-hybrid screening, we identified ICAT (inhibitor of β-catenin and Tcf4) as a novel Ptf1a interactor. ICAT regulates the Wnt pathway and cell proliferation. We validated and mapped the ICAT–Ptf1a interaction in vitro and in vivo. We demonstrated that, following its overexpression in acinar tumour cells, ICAT regulates negatively PTF1 activity in vitro and in vivo. This effect was independent of β-catenin and was mediated by direct binding to Ptf1a and displacement of P/CAF. ICAT also modulated the expression of Pdx1 and Sox9 in acinar tumour cells. ICAT overexpression reduced the interaction of Ptf1a with Rbpjl and P/CAF and impaired Ptf1a acetylation by P/CAF. ICAT did not affect the subcellular localization of Ptf1a. In human pancreas, ICAT displayed a cell-type-specific distribution; in acinar and endocrine cells, it was nuclear, whereas in ductal cells, it was cytoplasmic. In ductal adenocarcinomas, ICAT displayed mainly a nuclear or mixed distribution and the former was an independent marker of survival. ICAT regulates acinar differentiation and it does so through a novel Wnt pathway-independent mechanism that may contribute to pancreatic disease.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
May 2013
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
April 12 2013
ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression in tumours
M. Luisa Campos;
M. Luisa Campos
1
*Grupo de Carcinogénesis Epitelial, Programa de Patología Molecular, CNIO-Spanish National Cancer Research Center, 28029 Madrid, Spain
†Unitat de Biologia Cellular i Molecular, Institut Municipal d’Investigació Mèdica, 08003 Barcelona, Spain
Search for other works by this author on:
Víctor J. Sánchez-Arévalo Lobo;
Víctor J. Sánchez-Arévalo Lobo
1
*Grupo de Carcinogénesis Epitelial, Programa de Patología Molecular, CNIO-Spanish National Cancer Research Center, 28029 Madrid, Spain
Search for other works by this author on:
Annie Rodolosse;
Annie Rodolosse
†Unitat de Biologia Cellular i Molecular, Institut Municipal d’Investigació Mèdica, 08003 Barcelona, Spain
‡Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain
Search for other works by this author on:
Cara J. Gottardi;
Cara J. Gottardi
§Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, U.S.A.
Search for other works by this author on:
Andrea Mafficini;
Andrea Mafficini
¶ARC-NET The Miriam Cherubini-Applied Research on Cancer Center, 37134 Verona, Italy
Search for other works by this author on:
Stefania Beghelli;
Stefania Beghelli
¶ARC-NET The Miriam Cherubini-Applied Research on Cancer Center, 37134 Verona, Italy
Search for other works by this author on:
Maria Scardoni;
Maria Scardoni
∥Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy
Search for other works by this author on:
Claudio Bassi;
Claudio Bassi
**Department of Surgery and Oncology, University of Verona, 37134 Verona, Italy
Search for other works by this author on:
Aldo Scarpa;
Aldo Scarpa
¶ARC-NET The Miriam Cherubini-Applied Research on Cancer Center, 37134 Verona, Italy
∥Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy
Search for other works by this author on:
Francisco X. Real
Francisco X. Real
2
*Grupo de Carcinogénesis Epitelial, Programa de Patología Molecular, CNIO-Spanish National Cancer Research Center, 28029 Madrid, Spain
†Unitat de Biologia Cellular i Molecular, Institut Municipal d’Investigació Mèdica, 08003 Barcelona, Spain
‡Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain
2To whom correspondence should be addressed (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 05 2012
Revision Received:
December 20 2012
Accepted:
January 22 2013
Accepted Manuscript online:
January 22 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 451 (3): 395–405.
Article history
Received:
June 05 2012
Revision Received:
December 20 2012
Accepted:
January 22 2013
Accepted Manuscript online:
January 22 2013
Connected Content
A correction has been published:
ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression in tumours
Citation
M. Luisa Campos, Víctor J. Sánchez-Arévalo Lobo, Annie Rodolosse, Cara J. Gottardi, Andrea Mafficini, Stefania Beghelli, Maria Scardoni, Claudio Bassi, Aldo Scarpa, Francisco X. Real; ICAT is a novel Ptf1a interactor that regulates pancreatic acinar differentiation and displays altered expression in tumours. Biochem J 1 May 2013; 451 (3): 395–405. doi: https://doi.org/10.1042/BJ20120873
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |