scholarly journals Cell-type and promoter-context dependent retinoic acid receptor (RAR) redundancies for RAR beta 2 and Hoxa-1 activation in F9 and P19 cells can be artefactually generated by gene knockouts.

1996 ◽  
Vol 93 (12) ◽  
pp. 6197-6202 ◽  
Author(s):  
R. Taneja ◽  
B. Roy ◽  
J. L. Plassat ◽  
C. F. Zusi ◽  
J. Ostrowski ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
P19 Cells ◽  
Cell Type ◽  
Acid Receptor ◽  
Gene Knockouts ◽  
Beta 2 ◽  
Context Dependent

scholarly journals Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta) through direct interaction with RAR beta.

1995 ◽  
Vol 15 (11) ◽  
pp. 5868-5878 ◽  
Author(s):  
G E Folkers ◽  
P T van der Saag
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Direct Interaction ◽  
Activation Function ◽  
Acid Receptor ◽  
Adenovirus E1a ◽  
Beta 2 ◽  
Putative Zinc Finger ◽  
Zinc Finger Region ◽  
Receptor Beta

Transcription regulation by DNA-bound activators is thought to be mediated by a direct interaction between these proteins and TATA-binding protein (TBP), TFIIB, or TBP-associated factors, although occasionally cofactors or adapters are required. For ligand-induced activation by the retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer, the RAR beta 2 promoter is dependent on the presence of E1A or E1A-like activity, since this promoter is activated by retinoic acid only in cells expressing such proteins. The mechanism underlying this E1A requirement is largely unknown. We now show that direct interaction between RAR and E1A is a requirement for retinoic acid-induced RAR beta 2 activation. The activity of the hormone-dependent activation function 2 (AF-2) of RAR beta is upregulated by E1A, and an interaction between this region and E1A was observed, but not with AF-1 or AF-2 of RXR alpha. This interaction is dependent on conserved region III (CRIII), the 13S mRNA-specific region of E1A. Deletion analysis within this region indicated that the complete CRIII is needed for activation. The putative zinc finger region is crucial, probably as a consequence of interaction with TBP. Furthermore, the region surrounding amino acid 178, partially overlapping with the TBP binding region, is involved in both binding to and activation by AF-2. We propose that E1A functions as a cofactor by interacting with both TBP and RAR, thereby stabilizing the preinitiation complex.

scholarly journals Tissue-specific distribution of a novel C-terminal truncation retinoic acid receptor mutant which acts as a negative repressor in a promoter- and cell-type-specific manner.

1995 ◽  
Vol 15 (4) ◽  
pp. 1961-1967 ◽  
Author(s):  
T Matsui ◽  
S Sashihara
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Cell Type ◽  
F9 Cells ◽  
Acid Receptor ◽  
Retinoic Acid Response Element ◽  
Specific Distribution ◽  
Mouse Tissues ◽  
Specific Manner ◽  
Cell Type Specific

A cDNA clone which encodes a truncation form of the gamma subtype of the retinoic acid receptor (RAR gamma) has been isolated. The mutant RAR gamma (RAR gamma Bm382) has lost its 65 C-terminal amino acids, thus truncating a part of the dimerization and activation domains. By using a reverse transcription-coupled PCR technique, it was shown that RAR gamma Bm382 is expressed at different levels in various mouse tissues and that the level of its expression does not correlate with that of normal RAR gamma B. Cotransfection studies revealed that RAR gamma Bm382 acts as a repressor of normal RARs in a promoter- and cell-type-specific manner. Transcription of beta RARE and TREinv promoters was inhibited by RAR gamma Bm382 in both HeLa and F9 cells. Unlike these two promoters, however, RAR gamma Bm382 did not inhibit transcription of the TREpal promoter in HeLa cells but did so in F9 cells. Moreover, while transcription of the lamRARE promoter was inhibited by RAR gamma Bm382 in both HeLa and F9 cells, the inhibition was not observed when F9 cells were induced to differentiate with retinoic acid and dibutyryl cyclic AMP. DNA-binding analysis revealed that RAR gamma Bm382 is able to form a heterodimer with the retinoid X receptor and bind to the different types of retinoic acid response elements with almost the same efficiency as normal RAR. By comparison with effects of other truncation mutants created in vitro, it was suggested that the C-terminal end of the ligand binding domain of RAR is crucial for determining the specificity of transactivation by RAR. Given these observations, we discuss the possibility that protein factors which mediate retinoic acid response element- and cell-type-specific transactivation by RAR are present.

scholarly journals Stimulation of tissue-type plasminogen activator expression by retinoic acid in human endothelial cells requires retinoic acid receptor beta 2 induction

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 531-541 ◽  
Author(s):  
M Lansink ◽  
T Kooistra
Keyword(s):  
Endothelial Cells ◽  
Retinoic Acid ◽  
Plasminogen Activator ◽  
Retinoic Acid Receptor ◽  
Tissue Type ◽  
Mrna Levels ◽  
Tissue Type Plasminogen Activator ◽  
Acid Receptor ◽  
Type Plasminogen Activator ◽  
Beta 2

We previously showed the involvement of retinoic acid receptor alpha (RAR alpha) in the induction of tissue-type plasminogen activator (t- PA) synthesis by RA in human umbilical vein endothelial cells (HUVECs). However, the rather slow onset of this induction of t-PA synthesis suggested an indirect role of RAR alpha. Here, we show that the protein synthesis inhibitor, cycloheximide completely blocks the induction of t- PA by RA, which points to the need of an intermediary protein in t-PA stimulation. This intermediary protein is likely to be RAR beta 2 on the basis of the following findings: (1) the induction of RAR beta by RA exactly precedes that of t-PA; (2) HUVECs with elevated RAR beta mRNA levels show an undelayed t-PA induction on stimulation with RA, and this response can be almost completely inhibited with an RAR antagonist; and (3) an antisense oligodeoxynucleotide against the translation initiation site of RAR beta 2 mRNA greatly reduces the t-PA induction by RA. Thus, induction of t-PA by RA in HUVECs involves a 2- step mechanism requiring induction of RAR beta 2 via RAR alpha, followed by induction of t-PA synthesis via RAR beta 2. Each of these steps is shown to have a different activation profile with RA and 9 cis RA.

scholarly journals E1A functions as a coactivator of retinoic acid-dependent retinoic acid receptor-beta 2 promoter activation.

1993 ◽  
Vol 7 (4) ◽  
pp. 604-615
Author(s):  
F A Kruyt ◽  
G E Folkers ◽  
A J Walhout ◽  
B J van der Leede ◽  
P T van der Saag
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Promoter Activation ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Beta ◽  
Beta 2 ◽  
Receptor Beta
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