Regulation of inhibitors of differentiation family proteins by thyroid-stimulating hormone in FRTL-5 thyroid cells.
Members of the inhibitors of differentiation (Id) family of helix-loop-helix (HLH) proteins are known to play important roles in the proliferation and differentiation of many cell types. Thyroid-stimulating hormone (TSH) regulates proliferation and differentiation by activating TSH receptor (TSHR) in thyrocytes. In this study, we found that Id2, one of the Id family proteins, is a major target for regulation by TSH in FRTL-5 thyroid cells. TSH rapidly increases the Id2 mRNA level in FRTL-5 thyroid cells but the Id2 protein showed biphasic regulatory patterns, being transiently reduced and subsequently induced by TSH treatment. Transient reduction of Id2 protein was noted within 2 hr of TSH treatment and was mediated by proteasomal degradation. Moreover, reduced Id2 expression correlated with the activity of the phosphatidylinositol 3 kinase pathway, which is activated by TSH. Although TSH increases the activity of the Id2 promoter, TSH-induced activation of this promoter was independent of c-Myc. Id2 did not alter TTF-1- and Pax-8-mediated effects on the regulation of the Tg promoter. Thus, in summary, we found that TSH regulates Id2 expression, but that Id2 does not alter the expression of thyroid-specific genes, such as Tg, in FRTL-5 thyroid cells.
Jo
Young Suk
YS
Division of Endocrinology, Department of Internal Medicine, Eulji University School of Medicine, 640 Daesa-dong, Jung-gu, Daejeon, Korea.
Hwang
Eun Suk
ES
Lee
Ju Hee
JH
Lee
Yunhyeong
Y
Kim
Seul Young
SY
Choi
Yun-Sun
YS
Bai
Youn-Sun
YS
Hong
Jun Hwa
JH
Kim
Yun-Jeung
YJ
Lee
Ihn-Suk
IS
Rha
So Young
SY
Ro
Heung-kyu
HK
Shong
Minho
M
D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology*; D013972:Thyrotropin / Q000378:metabolism*
C497451:Id2 protein, rat; D051797:Inhibitor of Differentiation Protein 2; D007328:Insulin; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499497:Pax8 protein, rat; D016271:Proto-Oncogene Proteins c-myc; D013972:Thyrotropin; D013954:Thyroglobulin; D019869:Phosphatidylinositol 3-Kinases