Mutation of a Lysine Residue in a Homeodomain Generates Dominant Negative Thyroid Transcription Factor 1†

Biochemistry ◽  
2004 ◽  
Vol 43 (39) ◽  
pp. 12489-12497 ◽  
Author(s):  
Li Yang ◽  
Dong Yan ◽  
Molly Bruggeman ◽  
Hong Du ◽  
Cong Yan
Keyword(s):  
Transcription Factor ◽  
Lysine Residue ◽  
Dominant Negative ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

scholarly journals Thyroid Transcription Factor 1 Rescues PAX8/p300 Synergism Impaired by a Natural PAX8 Paired Domain Mutation with Dominant Negative Activity

2005 ◽  
Vol 19 (7) ◽  
pp. 1779-1791 ◽  
Author(s):  
Helmut Grasberger ◽  
Usanee Ringkananont ◽  
Paule LeFrancois ◽  
Marc Abramowicz ◽  
Gilbert Vassart ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Wild Type ◽  
Paired Domain ◽  
Thyroid Cells ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Abstract Mutations in the paired domain transcription factor PAX8 are a rare cause of congenital hypothyroidism due to thyroid dysgenesis. We identified a novel and unique PAX8 mutation segregating in seven affected members of a three-generations family. The mutation replaces an invariant serine residue within helix 2 of the paired DNA-binding domain for phenylalanine. The mutant protein (PAX8-S48F) does not induce the thyroglobulin promoter in nonthyroid cells, but displays almost half of wild-type PAX8 activity in thyroid cells. PAX8-S48F shows no defect in expression, nuclear targeting, or DNA binding and retains the ability to synergize with thyroid transcription factor 1 (TTF-1, NKX2.1). However, we found that in nonthyroid cells, the acetylation-independent synergism with the general transcriptional adaptor p300 is completely abrogated, suggesting that PAX8-S48F may be unable to efficiently recruit p300. Reconstitution experiments in nonthyroid cells reveal that TTF-1 can partially rescue PAX8-S48F/p300 synergism and thus reproduce the situation in thyroid cells. These functional characteristics result in a dominant negative effect of PAX8-S48F on coexpressed wild-type PAX8 activity, which is not observed in paired domain mutations with DNA binding defect. Our results describe the first dominant negative missense mutation in a paired domain and provide evidence for a crucial role of the p300 coactivator in mediating the functional synergism between PAX8 and TTF-1 in thyroid-specific gene expression.

scholarly journals Identification of Thyroid Transcription Factor-1 in C Cells and Parathyroid Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (6) ◽  
pp. 3014-3017 ◽  
Author(s):  
Koichi Suzuki ◽  
Yoshihiko Kobayashi ◽  
Ryohei Katoh ◽  
Leonard D. Kohn ◽  
Akira Kawaoi
Keyword(s):  
Transcription Factor ◽  
C Cells ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1

Thyroid transcription factor-1 expression in colorectal adenocarcinomas

2011 ◽  
Vol 207 (11) ◽  
pp. 686-690 ◽  
Author(s):  
Matthias Dettmer ◽  
Tae Eun Kim ◽  
Chan Kwon Jung ◽  
Eun Sun Jung ◽  
Kyo Young Lee ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1 ◽  
Colorectal Adenocarcinomas

Thyroid Transcription Factor 1 Immunohistochemistry as an Intraoperative Diagnostic Tool at Frozen Section for Distinction Between Primary and Secondary Lung Tumors

2007 ◽  
Vol 131 (4) ◽  
pp. 582-587
Author(s):  
David N. Butcher ◽  
Peter Goldstraw ◽  
George Ladas ◽  
Michael E. Dusmet ◽  
Mary N. Sheppard ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Frozen Section ◽  
Operative Procedure ◽  
Tumor Type ◽  
Diagnostic Confidence ◽  
Thyroid Transcription Factor 1 ◽  
Specificity And Sensitivity ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1 ◽  
Pulmonary Tumors

Abstract Context.—Intraoperative distinction between primary and metastatic carcinomas in the lung at frozen section remains problematic. Objective.—To assess the value and practicality of immunohistochemistry for thyroid transcription factor 1 at the time of intraoperative frozen section. Design.—Thirty-three patients presented with either a solitary pulmonary mass or 2 pulmonary masses and a history of carcinoma in a different organ. In addition to routine frozen section for assessment of tumor type, we looked for expression of thyroid transcription factor 1, using the EnVision system with abridged methodology. Results.—Ten cases were positive for thyroid transcription factor 1, which was confirmed on subsequent paraffin sections. Nine of these were confirmed as primary pulmonary adenocarcinomas, but 1 case proved to be a rare false-positive metastatic colonic carcinoma. Twenty-three cases were negative on frozen section and reported as favoring metastatic disease. In all cases, additional immunohistochemical data increased diagnostic confidence, but particularly in cases of positive primary pulmonary tumors and in cases with disease metastatic from sites other than the large bowel. The average time in addition to that of the basic frozen section was 24 minutes per test with a cost of £32 (US$57). Conclusions.—Frozen section immunohistochemistry for thyroid transcription factor 1 shows specificity and sensitivity similar to those seen for formalin-fixed tissues and is feasible within the time frame of a thoracotomy. Diagnostic confidence is increased, especially with positive primary pulmonary tumors. However, its practice should be properly planned within an operative procedure as liberal usage will likely have significant staff and cost implications.

scholarly journals Prognostic Value of Thyroid Transcription Factor-1 Expression in Patients with Advanced Lung Adenocarcinoma

In Vivo ◽  
2018 ◽  
Vol 32 (6) ◽  
pp. 1571-1579 ◽  
Author(s):  
ROLANDAS ZABLOCKIS ◽  
EDVARDAS ŽURAUSKAS ◽  
EDVARDAS DANILA ◽  
VYGANTAS GRUSLYS
Keyword(s):  
Transcription Factor ◽  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcription Factor 1
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