Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters.

Abstract

The Pax-8 gene, a member of the murine family of paired box-containing genes (Par genes), is expressed in adult thyroid and in cultured thyroid cell lines. The Pax-8 protein binds, through its paired domain, to the promoters of thyroglobulin and thyroperoxidase, genes that are exclusively expressed in the thyroid. In both promoters, the binding site of Pax-8 overlaps with that of TTF-l1, a homeodomain-containing protein involved in the activation of thyroid-specific transcription. Pax-8 activates transcription from cotransfected thyroperoxidase and thyroglobulin promoters, indicating that it may be involved in the establishment, control, or maintenance of the thyroid-differentiated phenotype. Thus, the promoters of thyroglobulin and thyroperoxidase represent the first identified natural targets for transcriptional activation by a paired domain-containing protein.

Concomitant activation of MEK-1 and Rac-1 increases the proliferative potential of thyroid epithelial cells, without affecting their differentiation

“…This process requires the expression of a set of cell-type-speci®c gene products, which include thyroglobulin (TG), thyroperoxidase (TPO), thyroidstimulating hormone receptor (TSH-R) and Na + /l 7 symporter (NIS) (Damante and Di Lauro, 1994). Studies on the TG and TPO promoters have allowed the identi®cation of three thyroid-speci®c transcription factors, TTF-1 (Thyroid Transcription Factor-1), TTF-2 (Thyroid Transcription Factor-2) and Pax-8 (belonging to the family of the paired domain proteins), involved in the onset and maintenance of the di erentiation status (Guazzi et al, 1990;Zannini et al, 1992Zannini et al, , 1997. These transcription factors are expressed during thyroid development, in the adult gland, as well as in a few other sites and their concomitant expression is unique to thyroid cells (Civitareale et al, 1989;Lazzaro et al, 1991;Missero et al, 1997;Zannini et al, 1997).…”

Thyroid Transcription Factor-1 in Normal, Hyperplastic, and Neoplastic Follicular Thyroid Cells Examined by Immunohistochemistry and Nonradioactive In Situ Hybridization

“…Four genes encoding thyroid-specific proteins have been cloned: thyroglobulin (Tg), thyroperoxidase (TPO), thyroid-stimulating hormone receptor (1), and, more recently, thyroid iodine transporter (2). This tissue-restricted protein production is regulated, at least in part, by the thyroid-specific nuclear factors, thyroid transcription factors 1 and 2 (TTF-1 and TTF-2) (3, 4) and Pax-8 (5). All of them bind to Tg and TPO promoters (5,6).…”

“…This tissue-restricted protein production is regulated, at least in part, by the thyroid-specific nuclear factors, thyroid transcription factors 1 and 2 (TTF-1 and TTF-2) (3, 4) and Pax-8 (5). All of them bind to Tg and TPO promoters (5,6). TTF-1 and Pax-8, however, preferentially bind to the Tg and TPO promoters, respectively (5).…”

“…All of them bind to Tg and TPO promoters (5,6). TTF-1 and Pax-8, however, preferentially bind to the Tg and TPO promoters, respectively (5). In addition, TTF-1 binds to the thyroid-stimulating hormone receptor gene promoter (7,8).…”

Co-operation between the PAI and RED subdomains of Pax-8 in the interaction with the thyroglobulin promoter

“…Pax-8 activates the promoters of the thyroglobulin (Tg) and thyroperoxidase (TPO) genes in the follicular thyroid cell, by interacting with sites located near the transcriptional start sites [18]. Both of these sites partially overlap with those of a different thyroid-specific transcription factor, TTF-1 ( Figure 1).…”