A novel DNA-binding motif in prostate tumor overexpressed-1 (PTOV1) required for the expression of ALDH1A1 and CCNG2 in cancer cells.

Autor: Maggio V; Biochemistry Service, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona, 08035, Spain., Cánovas V; Biochemistry Service, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona, 08035, Spain., Félix AJ; Department of Biochemistry and Physiology, School of Pharmacy, And Institute of Nanoscience and Nanotechnology, University of Barcelona, Avinguda Joan XXIII 27, 08028, Barcelona, Spain., Gómez V; Biochemistry Service, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona, 08035, Spain., de Torres I; Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain., Semidey ME; Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain., Morote J; Biochemistry Service, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona, 08035, Spain; Deparment of Urology, Vall d'Hebron University Hospital, and Universitat Autònoma de Barcelona, Spain., Noé V; Department of Biochemistry and Physiology, School of Pharmacy, And Institute of Nanoscience and Nanotechnology, University of Barcelona, Avinguda Joan XXIII 27, 08028, Barcelona, Spain., Ciudad CJ; Department of Biochemistry and Physiology, School of Pharmacy, And Institute of Nanoscience and Nanotechnology, University of Barcelona, Avinguda Joan XXIII 27, 08028, Barcelona, Spain., Paciucci R; Biochemistry Service, Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona, 08035, Spain. Electronic address: rosanna.paciucci@vhir.org.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2019 Jun 28; Vol. 452, pp. 158-167. Date of Electronic Publication: 2019 Mar 25.
DOI: 10.1016/j.canlet.2019.03.019
Abstrakt: PTOV1 is a transcription and translation regulator and a promoter of cancer progression. Its overexpression in prostate cancer induces transcription of drug resistance and self-renewal genes, and docetaxel resistance. Here we studied PTOV1 ability to directly activate the transcription of ALDH1A1 and CCNG2 by binding to specific promoter sequences. Chromatin immunoprecipitation and electrophoretic mobility shift assays identified a DNA-binding motif inside the PTOV-A domain with similarities to known AT-hooks that specifically interacts with ALDH1A1 and CCNG2 promoters. Mutation of this AT-hook-like sequence significantly decreased the expression of ALDH1A1 and CCNG2 promoted by PTOV1. Immunohistochemistry revealed the association of PTOV1 with mitotic chromosomes in high grade prostate, colon, bladder, and breast carcinomas. Overexpression of PTOV1, ALDH1A1, and CCNG2 significantly correlated with poor prognosis in prostate carcinomas and with shorter relapse-free survival in colon carcinoma. The previously described interaction with translation complexes and its direct binding to ALDH1A1 and CCNG2 promoters found here reveal the PTOV1 capacity to modulate the expression of critical genes at multiple levels in aggressive cancers. Remarkably, the AT-hook motifs in PTOV1 open possibilities for selective targeting its nuclear and/or cytoplasmic activities.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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