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- W2092810947 endingPage "4303" @default.
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- W2092810947 abstract "The avian erythroblastosis virus (AEV) oncoprotein v-ErbA represents a mutated, oncogenic thyroid hormone receptor alpha (c-ErbA/ TRalpha). v-ErbA cooperates with the stem cell factor-activated, endogenous receptor tyrosine kinase c-Kit to induce self-renewal and to arrest differentiation of primary avian erythroblasts, the AEV transformation target cells. In this cooperation, v-ErbA substitutes for endogenous steroid hormone receptor function required for sustained proliferation of non-transformed erythroid progenitors. In this paper, we propose a novel concept of how v-ErbA transforms erythroblasts. Using culture media strictly depleted from thyroid hormone (T3) and retinoids, the ligands for c-ErbA/TRalpha and its co-receptor RXR, we show that overexpressed, unliganded c-ErbA/ TRalpha closely resembles v-ErbA in its activity on primary erythroblasts. In cooperation with ligand-activated c-Kit, c-ErbA/ TRalpha causes steroid-independent, long-term proliferation and tightly blocks differentiation. Activation of c-ErbA/ TRalpha by physiological T3 levels causes the loss of self-renewal capacity and induces synchronous, terminal differentiation under otherwise identical conditions. This T3-induced switch in erythroid progenitor development is correlated with a decrease of c-ErbA-associated histone deacetylase activity. Our results suggest that the crucial role of the mutations activating v-erbA as an oncogene is to 'freeze' c-ErbA/ TRalpha in its non-liganded, repressive conformation and to facilitate its overexpression." @default.
- W2092810947 created "2016-06-24" @default.
- W2092810947 creator A5006188950 @default.
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- W2092810947 creator A5058031276 @default.
- W2092810947 creator A5060401985 @default.
- W2092810947 creator A5066055526 @default.
- W2092810947 date "1998-08-03" @default.
- W2092810947 modified "2023-09-25" @default.
- W2092810947 title "The thyroid hormone receptor functions as a ligand-operated developmental switch between proliferation and differentiation of erythroid progenitors" @default.
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- W2092810947 doi "https://doi.org/10.1093/emboj/17.15.4291" @default.
- W2092810947 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1170763" @default.
- W2092810947 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9687498" @default.