| Autor: |
Pemrick, S M, Abarzúa, P, Kratzeisen, C, Marks, M S, Medin, J A, Ozato, K, Grippo, J F |
| Předmět: |
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| Zdroj: |
Leukemia (08876924); Apr98, Vol. 12 Issue 4, p554-562, 9p |
| Abstrakt: |
The chimeric receptor, RARalpha/VDR, contains the DNA-binding domain of the retinoic acid receptor (RARalpha) and the ligand-binding domain of the vitamin D receptor (VDR). The ligand-binding properties of RARalpha/VDR are equivalent to that of VDR, with an observed Kd for 1alpha,25 dihydroxy-vitamin D3 (D3) of 0.5 nM. In CV-1 cells, both RARalpha and RARalpha/VDR induce comparable levels of ligand-mediated transcriptional activity from the retinoic acid responsive reporter gene, beta(RARE)3-TK-luciferase, in the presence of the ligand predicted from the receptor ligand-binding domain. Two chimeric RAR receptors were constructed which contained the ligand-binding domain of the estrogen receptor (ER): RARalpha/ER and ER/RARalpha/ER. Both RARalpha/ER and ER/RARalpha/ER bind beta-estradiol with high affinity, and are transcriptionally active only from palindromic RAREs (TREpal and/or (TRE3)3). Only RARalpha/VDR matched in kind and degree the functional characteristics of RARalpha: (1) maximally active from the beta(RARE); (2) moderately active from the TREs; (3) inactive from the retinoic X receptor response elements (RXREs) ApoA1 and CRBP II; (4) forms heterodimers with RXRalpha; and (5) binds to the betaRARE. F9 embryonal carcinoma cell lines were generated which express RARalpha/VDR mRNA (F9RARalpha/VDR cells) and compared with F9 wild-type (F9-Wt) cells, which do not express VDR mRNA. Treatment with all-trans retinoic acid (tRA) inhibits cell growth and induces the differentiation morphology in both F9-Wt and F9-RARalpha/VDR cells; whereas, treatment with D3 is similarly effective only for F9-RARalpha/VDR cells. It is concluded RARalpha/VDR is an useful 'tool' to pinpoint, or to augment transcription from RAREs in gene pathways controlled by RAR without inhibiting the retinoid responsiveness of endogenous RARs. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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