[26] Nuclear retinoic acid receptors: Cloning, analysis, and function

Pfahl, Magnus; Tzukerman, Maty; Zhang, Xiaokun; Lehmann, J.; Hermann, T; Wills, Ken N.; Graupner, Gerhart

doi:10.1016/0076-6879(90)89297-u

Cited by 75 publications

(37 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Determination of CAT activity was performed as previously described (Pfahl et al, 1990). The b-galactosidase activity was measured as previously described (Nilsen et al, 1983) to normalize for transfection eciency.…”

Section: Dna Transfections and Cat Assaysmentioning

confidence: 99%

Retinoic acid receptors and muscle b-HLH proteins: partners in retinoid-induced myogenesis

et al. 1998

View full text Add to dashboard Cite

The results reported here indicate that retinoic acid (RA) induces growth arrest and dierentiation only in MyoDexpressing muscle cells. Transient transfection assays reveal a functional interaction between MyoD, a key myogenic regulator and RA-receptors, principal mediators of RA actions. Interestingly, we demonstrate that RXR-MyoD-containing complexes are recruited at speci®c MyoD DNA-binding sites in muscle cells.Furthermore, we also demonstrate that RA-receptors and the muscle basic helix ± loop ± helix (b-HLH) proteins interact physically. Mutational analysis suggests that this interaction occurs via the basic region of muscle b-HLH proteins and the DNA-binding domain of RAreceptors and is important for functional interactions between these two families of transcription factors. In conclusion, these results highlight novel interactions between two distinct groups of regulatory proteins that in¯uence cell growth and dierentiation.

show abstract

Section: Dna Transfections and Cat Assaysmentioning

confidence: 99%

Retinoic acid receptors and muscle b-HLH proteins: partners in retinoid-induced myogenesis

et al. 1998

View full text Add to dashboard Cite

show abstract

“…After 12 h, the cells were lysed and subjected to luciferase activity assay using a luciferase assay system (Promega) in a luminometer. Relative luciferase activity was normalized to ␤-galactosidase activity, which was measured as described previously (34).…”

Section: Methodsmentioning

confidence: 99%

The Farnesyltransferase Inhibitor Lonafarnib Induces CCAAT/Enhancer-binding Protein Homologous Protein-dependent Expression of Death Receptor 5, Leading to Induction of Apoptosis in Human Cancer Cells

Sun

Liu

Zou

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Pre-clinical studies have demonstrated that farnesyltransferase inhibitors (FTIs) induce growth arrest or apoptosis in various human cancer cells independently of Ras mutations. However, the underlying mechanism remains unknown. Death receptor 5 (DR5) is a pro-apoptotic protein involved in mediating the extrinsic apoptotic pathway. Its role in FTI-induced apoptosis has not been reported. In this study, we investigated the modulation of DR5 by the FTI lonafarnib and the involvement of DR5 up-regulation in FTI-induced apoptosis. Lonafarnib activated caspase-8 and its downstream caspases, whereas the caspase-8-specific inhibitor benzyloxycarbonyl-Ile-Glu(methoxy)-Thr-Asp(methoxy)-fluoromethyl ketone or small interfering RNA abrogated lonafarnib-induced apoptosis, indicating that lonafarnib induces caspase-8-dependent apoptosis. Lonafarnib up-regulated DR5 expression, increased cell-surface DR5 distribution, and enhanced tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Overexpression of a dominant-negative Fas-associated death domain mutant or silencing of DR5 expression using small interfering RNA attenuated lonafarnib-induced apoptosis. These results indicate a critical role of the DR5-mediated extrinsic apoptotic pathway in lonafarnib-induced apoptosis. By analyzing the DR5 promoter, we found that lonafarnib induced a CCAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter. Lonafarnib increased CHOP expression, whereas silencing of CHOP expression abrogated lonafarnib-induced DR5 expression. These results thus indicate that lonafarnib induces CHOP-dependent DR5 up-regulation. We conclude that CHOP-dependent DR5 up-regulation contributes to lonafarnib-induced apoptosis.Farnesyltransferase inhibitors (FTIs) 3 are a class of agents that suppress the farnesyltransferase enzyme to prevent farnesylation of certain proteins such as the Ras oncoprotein (1, 2). These agents inhibit proliferation and induce apoptosis in various cancer cell lines in culture or suppress the growth of xenografts in nude mice with limited toxicity (1, 2). In the clinic, FTIs are well tolerated and have some positive outcomes in certain settings such as hematological malignancies and breast cancer, although the response rates to FTIs alone are generally poor. When combined with other therapeutic agents or radiotherapy, FTIs exhibit some encouraging clinical responses (1, 2).Lonafarnib (LNF; also called SCH66336 and Sarasar), a nonpeptide tricyclic FTI, was one of the first FTIs to undergo clinical testing and to exhibit significant activity (3). In vitro, this agent, either alone or in combination with other therapeutic agents, inhibits the growth or induces apoptosis of several types of human cancer cells (4 -12). In animal models, LNF demonstrates potent oral activity in a wide array of human tumor xenograft models including tumors of colon, lung, pancreas, prostate, and urinary bladder origin (12). When LNF is combined with other chemotherapeutic agents, enhanced anti...

show abstract

“…After 24 h, luciferase activity was measured using luciferase assay system (Promega) using a luminometer. Relative luciferase activity was normalized to b-gal activity, which was measured as described previously (Pfahl et al, 1990).…”

Section: Emsamentioning

confidence: 99%

Evidence that the human death receptor 4 is regulated by activator protein 1

et al. 2002

View full text Add to dashboard Cite

Death receptor 4 (DR4; also called TRAIL-R1), a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that triggers the apoptotic machinery upon binding to its ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Although several chemotherapeutic agents were reported to induce DR4 expression, the mechanism of this e ect remains largely unknown. To begin to understand its regulation, we cloned a 1.8 Kb 5'-flanking region of the human DR4 gene and identi®ed several putative binding sites for transcription factors including activator protein 1 (AP-1). Among the three putative AP-1 binding sites, the site located at 7350/7344 is functionally active as evidenced by a combination of electrophoretic mobility shift and luciferase reporter assays. The AP-1 activator phorbol 12 ± myristate 13-acetate (TPA) enhanced the binding of this DR4 AP-1 binding site to protein(s) in a nuclear extract from TPAtreated cells, increased luciferase activity of a reporter construct containing this site and induced DR4 expression at the transcription level. These results indicate that AP-1 regulates DR4 expression via the AP-1 binding site located at 7350/7344. AP-1 has been implicated in many critical cellular processes including apoptosis, and is a major target of the c-Jun NH 3 -terminal kinase signaling pathway that is activated by many anticancer drugs. Therefore, our ®ndings may increase the understanding of the mechanisms underlying AP-1-mediated apoptosis as well as drug-induced apoptosis.

show abstract

[26] Nuclear retinoic acid receptors: Cloning, analysis, and function

Cited by 75 publications

References 17 publications

Retinoic acid receptors and muscle b-HLH proteins: partners in retinoid-induced myogenesis

Retinoic acid receptors and muscle b-HLH proteins: partners in retinoid-induced myogenesis

The Farnesyltransferase Inhibitor Lonafarnib Induces CCAAT/Enhancer-binding Protein Homologous Protein-dependent Expression of Death Receptor 5, Leading to Induction of Apoptosis in Human Cancer Cells

Evidence that the human death receptor 4 is regulated by activator protein 1

Contact Info

Product

Resources

About