PMID- 10976919
OWN - NLM
STAT- MEDLINE
DCOM- 20010105
LR  - 20131121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 14
IP  - 9
DP  - 2000 Sep
TI  - Cross-talk between signal transducer and activator of transcription (Stat5) and 
      thyroid hormone receptor-beta 1 (TRbeta1) signaling pathways.
PG  - 1411-24
AB  - PRL and T3 are involved in antagonistic regulations during various developmental 
      processes in vertebrate species. We have studied cross-talk between transcription 
      factors activated by these signaling pathways, i.e. signal transducer and 
      activator of transcription 5 (Stat5) and thyroid hormone receptor beta1 
      (TRbeta1). Liganded TRbeta1 in the presence of its heterodimeric partner, 
      retinoid X receptor gamma (RXRgamma), inhibited the PRL-induced Stat5a- and 
      Stat5b-dependent reporter gene expression by up to 60%. This T3-inhibitory effect 
      studied on Stat5 activity was partly reversed by overexpression of a TRbeta1 
      dominant negative variant mutated within its nuclear localization signal (TR2A). 
      We next showed that TRbeta1 and TR2A in the presence of RXRgamma increased and 
      decreased, respectively, Stat5 localization into the nucleus regardless of 
      hormonal stimulation. Thus, our data suggest that TRbeta1 can be associated with 
      Stat5 in the cytoplasm and may be involved in Stat5 nuclear translocation. In 
      PRL-treated cells overexpressing TRbeta1/RXRgamma, both Stat5 and TRbeta1 were 
      coimmunoprecipitated, indicating physical association of the two transcription 
      factors. In these cells, addition of T3 with ovine (o)PRL decreased the amounts 
      of total and tyrosine-phosphorylated Stat5 in the cytoplasm compared with 
      oPRL-treated cells. In the nucleus, no clear difference was observed on Stat5 
      DNA-binding after treatment with PRL and T3 vs. PRL alone in TRbeta1/RXRgamma 
      transfected cells. However, antibodies directed against TRbeta1 lowered Stat5-DNA 
      binding and addition of the deacetylase inhibitor trichostatin A (TSA) relieved 
      T3 inhibition on Stat5 transcriptional activity. Thus, we postulated that the 
      negative cross-talk between TR and Stat5 on target genes could involve histone 
      deacetylase recruitment by liganded TRbeta1.
FAU - Favre-Young, H
AU  - Favre-Young H
AD  - INSERM Unite 344, Endocrinologie Moleculaire, Faculte de Medecine Necker, Paris, 
      France.
FAU - Dif, F
AU  - Dif F
FAU - Roussille, F
AU  - Roussille F
FAU - Demeneix, B A
AU  - Demeneix BA
FAU - Kelly, P A
AU  - Kelly PA
FAU - Edery, M
AU  - Edery M
FAU - de Luze, A
AU  - de Luze A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Histones)
RN  - 0 (Milk Proteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (STAT5A protein, human)
RN  - 0 (STAT5B protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 9002-62-4 (Prolactin)
SB  - IM
MH  - Cell Line
MH  - Cell Nucleus/physiology
MH  - Cytosol/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Genes, Reporter
MH  - Histones/metabolism
MH  - Humans
MH  - *Milk Proteins
MH  - Prolactin/pharmacology
MH  - Receptor Cross-Talk/*physiology
MH  - Receptors, Retinoic Acid/*physiology
MH  - Receptors, Thyroid Hormone/*physiology
MH  - Recombinant Fusion Proteins/metabolism
MH  - Retinoid X Receptors
MH  - STAT5 Transcription Factor
MH  - Signal Transduction/drug effects/*physiology
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/*physiology
MH  - Transcription, Genetic/drug effects/physiology
MH  - Transfection
MH  - Triiodothyronine/pharmacology
MH  - Tumor Suppressor Proteins
EDAT- 2000/09/08 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/08 11:00
PHST- 2000/09/08 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/08 11:00 [entrez]
AID - 10.1210/mend.14.9.0525 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2000 Sep;14(9):1411-24. doi: 10.1210/mend.14.9.0525.