HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0056v1 41/5/379    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Di Palma, T. Articles by Zannini, M. PubMed PubMed Citation Articles by Di Palma, T. Articles by Zannini, M.

T Di Palma, Istituto di Endocrinologia e Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Napoli, Italy
T de Cristofaro, Istituto di Endocrinologia e Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Napoli, Italy
C D'Ambrosio, ISPAAM, Consiglio Nazionale delle Ricerche, Napoli, Italy
D Del Prete, Istituto di Endocrinologia e Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Napoli, Italy
A Scaloni, ISPAAM, Consiglio Nazionale delle Ricerche, Napoli, Italy
M Zannini, Istituto di Endocrinologia e Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Napoli, 80131, Italy

Correspondence: Mariastella Zannini, Email: s.zannini{at}ieos.cnr.it

Abstract

Pax8 is a transcription factor that plays an important role in the regulation of genes that are exclusively expressed in differentiated thyroid cells. In the thyroid cell environment, evidence exists that Pax8 is part of a multiprotein complex in which its transcriptional activity may be modulated by specific co-factors. In the attempt to identify proteins able to interact with Pax8, we performed pull down experiments challenging the GST-Pax8 fusion protein with protein extracts prepared from the thyroid differentiated cell line PC Cl3. By this approach we isolated a 113-kDa protein able to associate with Pax8, which was further identified by mass fingerprint experiments as poly(ADP-ribose) polymerase-1 (PARP-1). To further confirm this interaction, we also showed that PARP-1 can be co-immunoprecipitated with Pax8 in vivo from a thyroid cell extract. Gel-shifts experiments demonstrated that PARP-1 binding to Pax8 significantly inhibits Pax8 binding to DNA. Accordingly, we provide evidence that the functional outcome of such an interaction is a significant downregulation of Pax8 transcriptional activity. In the context of thyroid-specific gene transcription, our results suggest that PARP-1 behaves as an important negative co-factor involved in the regulation of Pax8-dependent gene expression.