PMID- 10490654
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 10
DP  - 1999 Oct
TI  - NRIF3 is a novel coactivator mediating functional specificity of nuclear hormone 
      receptors.
PG  - 7191-202
AB  - Many nuclear receptors are capable of recognizing similar DNA elements. The
      molecular event(s) underlying the functional specificities of these receptors (in
      regulating the expression of their native target genes) is a very important issue
      that remains poorly understood. Here we report the cloning and analysis of a
      novel nuclear receptor coactivator (designated NRIF3) that exhibits a distinct
      receptor specificity. Fluorescence microscopy shows that NRIF3 localizes to the
      cell nucleus. The yeast two-hybrid and/or in vitro binding assays indicated that 
      NRIF3 specifically interacts with the thyroid hormone receptor (TR) and retinoid 
      X receptor (RXR) in a ligand-dependent fashion but does not bind to the retinoic 
      acid receptor, vitamin D receptor, progesterone receptor, glucocorticoid
      receptor, or estrogen receptor. Functional experiments showed that NRIF3
      significantly potentiates TR- and RXR-mediated transactivation in vivo but has
      little effect on other examined nuclear receptors. Domain and mutagenesis
      analyses indicated that a novel C-terminal domain in NRIF3 plays an essential
      role in its specific interaction with liganded TR and RXR while the N-terminal
      LXXLL motif plays a minor role in allowing optimum interaction. Computer modeling
      and subsequent experimental analysis suggested that the C-terminal domain of
      NRIF3 directly mediates interaction with liganded receptors through an LXXIL (a
      variant of the canonical LXXLL) module while the other part of the NRIF3 protein 
      may still play a role in conferring its receptor specificity. Identification of a
      coactivator with such a unique receptor specificity may provide new insight into 
      the molecular mechanism(s) of receptor-mediated transcriptional activation as
      well as the functional specificities of nuclear receptors.
FAU - Li, D
AU  - Li D
AD  - Division of Molecular Endocrinology, Departments of Medicine and Pharmacology,
      Skirball Institute of Biomolecular Medicine, New York University School of
      Medicine, New York, New York 10016, USA.
FAU - Desai-Yajnik, V
AU  - Desai-Yajnik V
FAU - Lo, E
AU  - Lo E
FAU - Schapira, M
AU  - Schapira M
FAU - Abagyan, R
AU  - Abagyan R
FAU - Samuels, H H
AU  - Samuels HH
LA  - eng
GR  - P30 CA016087/CA/NCI NIH HHS/United States
GR  - T35 DK007421/DK/NIDDK NIH HHS/United States
GR  - F32 DK009581/DK/NIDDK NIH HHS/United States
GR  - DK16636/DK/NIDDK NIH HHS/United States
GR  - DK09581/DK/NIDDK NIH HHS/United States
GR  - R01 DK016636/DK/NIDDK NIH HHS/United States
GR  - R56 DK016636/DK/NIDDK NIH HHS/United States
GR  - GM5541808/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (ITGB3BP protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cell Compartmentation
MH  - Computer Simulation
MH  - Gene Library
MH  - HeLa Cells
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Receptors, Thyroid Hormone/*metabolism
MH  - Retinoid X Receptors
MH  - Sequence Analysis, DNA
MH  - Transcription Factors/*metabolism
MH  - *Transcriptional Activation
MH  - Two-Hybrid System Techniques
PMC - PMC84712
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - 10.1128/mcb.19.10.7191 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Oct;19(10):7191-202. doi: 10.1128/mcb.19.10.7191.