Embryonal Long Terminal Repeat-Binding Protein Is a Murine Homolog of FTZ-F1, a Member of the Steroid Receptor Superfamily

Tsukiyama, Toshio; Ueda, Hitoshi; Hirose, Susumu; Niwa, Ohtsura

doi:10.1128/mcb.12.3.1286-1291.1992

Molecular and Cellular Biology

1992

DOI: 10.1128/mcb.12.3.1286-1291.1992

|View full text |Cite

Embryonal Long Terminal Repeat-Binding Protein Is a Murine Homolog of FTZ-F1, a Member of the Steroid Receptor Superfamily

Toshio Tsukiyama

Hitoshi Ueda

Susumu Hirose

et al.

Abstract: The embryonal long terminal repeat-binding protein, ELP, is present in undifferentiated mouse embryonal carcinoma cells. It binds to and suppresses transcription of the Moloney leukemia virus long terminal repeat in undifferentiated murine embryonal carcinoma cells. We report here that ELP is a mouse homolog of Drosophila FTZ-F1, which positively regulates transcription of the fushi tarazu gene in blastoderm-stage embryos of the fly. As members of the steroid receptor superfamily, ELP and FTZ-F1 have both DNA … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1998

2018

Publication Types

Select...

Article5

Relationship

Self Cite0

Independent5

Authors

Journals

Cited by 9 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10.1021/acs.biochem.8b00069.Five supplementary figures (PDF) Department of Molecular Biosciences, Northwestern University, 2205 Tech Dr., Evanston, IL 60208-3500. Telephone: +1 847-467-1173.…”

mentioning

confidence: 99%

Solution Nuclear Magnetic Resonance Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveal a Dynamic Helix in the Ligand-Binding Pocket

et al. 2018

View full text Add to dashboard Cite

The ligand-binding domains (LBDs) of the NR5A subfamily of nuclear receptors activate transcription via ligand-dependent and ligand-independent mechanisms. The Drosophila Ftz-F1 receptor (NR5A3) belongs to the latter category, and its ligand independence is attributed to a short helical segment (α6) within the protein that resides in the canonical ligand-binding pocket (LBP) in the crystalline state. Here, we show that the α6 helix is dynamic in solution when Ftz-F1 is bound to the LxxLL motif of its cofactor Ftz, undergoing motions on the fast (picosecond to nanosecond) as well as slow (microsecond to millisecond) time scales. Motions on the slow time scale (∼10 s) appear to pervade throughout the domain, most prominently in the LBP and residues at or near the cofactor-binding site. We ascribe the fast time scale motions to a solvent-accessible conformation for the α6 helix akin to those described for its orthologs in higher organisms. We assign this conformation where the LBP is "open" to a lowly populated species, while the major conformer bears the properties of the crystal structure where the LBP is "closed". We propose that these conformational transitions could allow binding to small molecule ligands and/or play a role in dissociation of the cofactor from the binding site. Indeed, we show that the Ftz-F1 LBD can bind phospholipids, not unlike its orthologs. Our studies provide the first detailed insights into intrinsic motions occurring on a variety of time scales in a nuclear receptor LBD and reveal that potentially functionally significant motions pervade throughout the domain in solution, despite evidence to the contrary implied by the crystal structure.

show abstract

mentioning

confidence: 99%

Solution Nuclear Magnetic Resonance Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveal a Dynamic Helix in the Ligand-Binding Pocket

et al. 2018

View full text Add to dashboard Cite

show abstract

Variant-type PML-RARα fusion transcript in acute promyelocytic leukemia: Use of a cryptic coding sequence from intron 2 of the RAR α gene and identification of a new clinical subtype resistant to retinoic acid therapy

Xiong

Zhou

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The physiologic actions of retinoic acids (RAs) are mediated through RA receptors (RARs) and retinoid X receptors (RXRs). The RAR␣ gene has drawn particular attention because it is the common target in all chromosomal translocations in acute promyelocytic leukemia (APL), a unique model in cancer research that responds to the effect of RA. In the great majority of patients with APL, RAR␣ is fused to the PML gene as a result of the t(15;17) translocation. Three distinct types of PML-RAR␣ transcripts, long (L), short (S), and variant (V), were identified. The V-type is characterized by truncation of exon 6 of PML and in some cases by the insertion of a variable ''spacer'' sequence between the truncated PML and RAR␣ mRNA fusion partners, although the precise mechanisms underlying formation of the V-type transcript remain unclear. To get further insights into the molecular basis of the t(15;17), we sequenced the entire genomic DNA region of RAR␣. Of note, all previously reported ''spacer'' sequences in V-type transcripts were found in intron 2 of the RAR␣ gene and most of these sequences were flanked by gt splice donor sites. In most cases, these ''cryptic'' coding sequences maintained the ORF of the chimeric transcript. Interestingly, two cases with a relatively long spacer sequence showed APL cellular and clinical resistance to RA treatment. In these cases, the aberrant V-type PML-RAR␣ protein displayed increased affinity to the nuclear corepressor protein SMRT, providing further evidence that RA exerts the therapeutic effect on APL through modulation of the RAR-corepressor interaction. Finally, among patients with the L-or S-type PML-RAR␣ fusion transcript, some consensus motifs were identified at the hotspots of the chromosome 17q breakpoints within intron 2 of RAR␣, strengthening the importance of this intron in the molecular pathogenesis of APL. R etinoic acids (RAs) play a wide variety of physiological roles during embryogenesis and adult life. The effects of RAs are mediated through two families of nuclear receptors, RA receptors (RARs) and retinoid X receptors (RXRs), each including three members, ␣, ␤, and ␥. Whereas RXRs can form homodimers, RARs need to heterodimerize with RXRs to constitute a functional receptor. These receptors bind to DNA motifs known as RAREs (RA response elements), located in the regulatory sequences of RA target genes (1). The transregulatory properties of RAR͞RXR are determined, in a ligand-dependent manner, by their interaction with two protein complexes, nuclear receptor corepressor (CoR) and coactivator (2). Each member of the RAR and RXR families is encoded by a unique gene, which may generate a number of isoforms with distinct N-terminal sequences through alternative use of 5Ј exons (3). The combinatorial expression of both gene families, as well as their isoforms, varies across different tissue͞cell types at distinct stages of development, contributing to the biological complexity of RA signaling (1-4).Over the last decade, the biomedical importance of RAR␣ has been highlight...

show abstract

Replication of enhancer-deficient amphotropic murine leukemia virus in human cells

Reuss¹,

Berdel²,

Ploss³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Embryonal Long Terminal Repeat-Binding Protein Is a Murine Homolog of FTZ-F1, a Member of the Steroid Receptor Superfamily

Cited by 9 publications

References 42 publications

Solution Nuclear Magnetic Resonance Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveal a Dynamic Helix in the Ligand-Binding Pocket

Solution Nuclear Magnetic Resonance Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveal a Dynamic Helix in the Ligand-Binding Pocket

Variant-type PML-RARα fusion transcript in acute promyelocytic leukemia: Use of a cryptic coding sequence from intron 2 of the RAR α gene and identification of a new clinical subtype resistant to retinoic acid therapy

Replication of enhancer-deficient amphotropic murine leukemia virus in human cells

Contact Info

Product

Resources

About