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-08-0010v1 41/3/177    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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pietrzak, M. Articles by Puzianowska-Kuznicka, M. Search for Related Content PubMed PubMed Citation Articles by Pietrzak, M. Articles by Puzianowska-Kuznicka, M.

M Pietrzak, Department of Endocrinology, Medical Research Center, Warsaw, Poland
M Puzianowska-Kuznicka, Department of Endocrinology, Medical Research Center, Warsaw, 02-106, Poland

Correspondence: Monika Puzianowska-Kuznicka, Email: monika{at}amwaw.edu.pl

Abstract

Triiodothyronine (T3) regulates apoptosis in cells according to their developmental stage, cell type, and patho-physiological state. The molecular mechanisms of this regulation, however, have been largely unknown. In this work we show that the expression of the MCL-1 protein, an anti-apoptotic member of BCL-2 family, increases in thyroid hormone receptor-expressing HK2 cells upon 6 h incubation in 100nM T3; we also describe the molecular mechanisms leading to this phenomenon. Transcription regulation assays performed in HEK 293 cells show that 100nM T3 increases transcription from the MCL-1 promoter 2-fold in the presence of thyroid hormone receptor β1, but not of its 1 isoform. However, this increase is not a result of direct activation via the thyroid hormone response element, TRE-DR4, located at the -998 to -983 position in this promoter; furthermore, the presence of 9-cis retinoic acid receptor is not required. The promoter's activation is abolished in the presence of phosphatidylinositol 3 kinase inhibitor, Wortmannin. The -295 to -107 promoter fragment contains all sequences involved in T3-dependent activation of the MCL-1 promoter, and cAMP responsive element located at the -262 to -255 position is a major mediator in this process. Therefore, MCL-1 expression is activated by T3 that increases its promoter activity by non-genomic mechanism using the phosphatidylinositol 3 kinase signal transduction pathway. We propose that this is another mechanism by which T3 regulates apoptosis.