Molecular Mechanisms of Action of Steroid/Thyroid Receptor Superfamily Members

Tsai, Ming‐Jer; O’Malley, Bert W.

doi:10.1146/annurev.bi.63.070194.002315

Cited by 2,731 publications

(1,315 citation statements)

References 0 publications

Supporting

Mentioning

1,276

Contrasting

Unclassified

Order By: Relevance

“…24 The synthetic glucocorticoid DEX has been used in the treatment of lymphoid leukemia and lymphoma and the mechanism underlying this treatment is the induction of apoptosis. 25 However, DEX can inhibit apoptosis in some cells such as neutrophils and tumors.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP

Namkoong

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-a plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondriadependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP

Namkoong

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…Thus, direct TH action on neuronal differentiation genes may be responsible for at least some of the known effects of TH on amphibian neuronal development such as its promotion of cytodifferentiation in the lateral motor column (Beaudoin, 1956;Race, 1961;Reynolds, 1963;Hughes, 1966;Decker, 1976) and other parts of the nervous system (reviewed in Kollros, 1981;Denver, 1998). However, it is currently unknown, which THresponsive genes are instrumental in mediating these effects in amphibians, even though several neuronspecific TH-responsive genes (Denver et al, 1997;Denver, 1998) Tsai and O'Malley, 1994;Shi et al, 1996Shi et al, , 1998Tata, 1996;Zhang and Lazar, 2000;Wu and Koenig, 2000). Effective DNA binding requires dimerization with other nuclear receptors, preferrably retinoid X receptors (RXR; reviewed in Zhang and Pfahl, 1993;Shi et al, 1996Shi et al, , 1998Tata, 1996;Zhang and Lazar, 2000;Wu and Koenig, 2000).…”

Section: Thyroid Hormones Promote Neurogenesis In the Spinal Cordmentioning

confidence: 99%

“…tors, which act as transcriptional activators after TH binding (reviewed in Tsai and O'Malley, 1994;Shi et al, 1996Shi et al, , 1998Tata, 1996;Wolffe and Shi, 1999;Zhang and Lazar, 2000), the close temporal correlation of xTR␣ up-regulation with the onset of larval neurogenesis in the spinal cord leads us to hypothesize that TH signaling may be involved in regulating neurogenesis in the Xenopus spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormone promotes neurogenesis in the Xenopus spinal cord

Schlosser

Koyano-Nakagawa

Kintner

2002

Developmental Dynamics

View full text Add to dashboard Cite

Three phases of neurogenesis can be recognized during Xenopus spinal cord development. An early peak during gastrulation/ neurulation is followed by a phase of low level neurogenesis throughout the remaining embryonic stages and a later peak at early larval stages. We show here that several genes known to be essential for early neurogenesis (X-NGNR-1, XNeuroD, XMyT1, X-Delta-1) are also expressed during later phases of neurogenesis in the spinal cord, suggesting that they are involved in regulating spinal neurogenesis at later stages. However, additional neuronal determination genes may be important during larval stages, because X-NGNR-1 shows only scant expression in the spinal cord during larval stages. Thyroid hormone treatment of early larvae promotes neurogenesis in the spinal cord, where thyroid hormone receptor xTR␣ is expressed from early larval stages onward and results in precocious up-regulation of XNeuroD, XMyT1, and N-Tubulin expression. Similarly, thyroid hormone treatments of Xenopus embryos, which were coinjected with xTR␣ and the retinoid X receptor xRXR␣, repeatedly resulted in increased numbers of neurons, whereas unliganded receptors repressed neurogenesis. Our findings show that thyroid hormones are sufficient to up-regulate neurogenesis in the Xenopus spinal cord.

show abstract

“…Similarly, GATA-2 interacts via its zinc finger motif with the bZip proteins, JUN and FOS (Kawana et al, 1995). Moreover, one of the two Cys 2 /Cys 2 -type zinc fingers of steroid hormone receptors functions in dimerization and in the formation of heterodimers (Tsai and O'Malley, 1994). These findings indicate that the zinc fingers of DNA-binding proteins can participate in significant protein-protein interactions.…”

Section: Introductionmentioning

confidence: 97%

Two distinct protein–protein interactions between the NIT2 and NMR regulatory proteins are required to establish nitrogen metabolite repression in Neurospora crassa

Pan

Feng

Marzluf

1997

Molecular Microbiology

View full text Add to dashboard Cite

SummaryNitrogen metabolism is a highly regulated process in Neurospora crassa. The structural genes that encode nitrogen catabolic enzymes are subject to nitrogen metabolite repression, mediated by the positive-acting NIT2 protein and by the negative-acting NMR protein. NIT2, a globally acting factor, is a member of the GATA family of regulatory proteins and has a single Cys 2 / Cys 2 zinc finger DNA-binding domain. The negativeacting NMR protein interacts via specific proteinprotein binding with two distinct regions of the NIT2 protein, a short alpha-helical motif within the NIT2 DNA-binding domain and a second motif at its carboxy terminus. Deletions of segments of NIT2 throughout most of its length result in truncated proteins, which are still functional for activating gene expression; most of these mutant NIT2 proteins still allow proper nitrogen repression of nitrate reductase synthesis. In contrast, deletions or certain amino acid substitutions within the zinc finger and the carboxy-terminal tail result in a loss of nitrogen metabolite repression. Those mutated forms of NIT2 that are insensitive to nitrogen repression have also lost one of the NIT2-NMR protein-protein interactions. These results provide compelling evidence that the specific NIT2-NMR interactions have a regulatory function and play a central role in establishing nitrogen metabolite repression.

show abstract

Molecular Mechanisms of Action of Steroid/Thyroid Receptor Superfamily Members

Cited by 2,731 publications

References 0 publications

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP

Thyroid hormone promotes neurogenesis in the Xenopus spinal cord

Two distinct protein–protein interactions between the NIT2 and NMR regulatory proteins are required to establish nitrogen metabolite repression in Neurospora crassa

Contact Info

Product

Resources

About