PMID- 8530518
OWN - NLM
STAT- MEDLINE
DCOM- 19960130
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 51
DP  - 1995 Dec 22
TI  - Enhancement of HL-60 differentiation by a new class of retinoids with selective 
      activity on retinoid X receptor.
PG  - 30765-72
AB  - Cellular responsiveness to retinoic acid and its metabolites is conferred through 
      two distinct families of receptors: the retinoic acid receptors (RARs) and the 
      retinoid X receptors (RXRs). Herein, we report on the identification and 
      characterization of several conformationally restricted retinoids, which 
      selectively bind and activate RX receptors. Under the influence of retinoids, 
      HL-60 myelocytic leukemia cells differentiate into granulocytes. This effect is 
      mediated by RAR alpha, as has been demonstrated through the use of a selective 
      RAR alpha antagonist (Apfel, C., Bauer, F., Crettaz, M., Forni, L., Kamber, M., 
      Kaufmann, F., LeMotte, P., Pirson, W., and Klaus, M. (1992) Proc. Natl. Acad. 
      Sci. U.S.A. 89, 7129-7133). Here, we show that conformationally restricted 
      RXR-specific retinoids, at doses that are per se inactive, are able to potentiate 
      by up to one order of magnitude the pro-differentiating effects of all-trans 
      retinoic acid and an RAR alpha-selective synthetic retinoid. We also present 
      evidence that these RXR-selective ligands are able to bind to a DNA RXR.RAR 
      heterodimer complex. This finding demonstrates that agonists for RARs and RXRs 
      can synergistically promote HL-60 differentiation, which could be mediated 
      through a heterodimer of these receptors.
FAU - Apfel, C M
AU  - Apfel CM
AD  - Department of Dermatology, F. Hoffmann-LaRoche, Basel, Switzerland.
FAU - Kamber, M
AU  - Kamber M
FAU - Klaus, M
AU  - Klaus M
FAU - Mohr, P
AU  - Mohr P
FAU - Keidel, S
AU  - Keidel S
FAU - LeMotte, P K
AU  - LeMotte PK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Binding, Competitive
MH  - Cell Differentiation/drug effects/*physiology
MH  - DNA, Complementary
MH  - HL-60 Cells
MH  - Humans
MH  - Kinetics
MH  - Molecular Structure
MH  - Receptors, Retinoic Acid/biosynthesis/drug effects/*physiology
MH  - Recombinant Proteins/biosynthesis/drug effects/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptors
MH  - Retinoids/metabolism/*pharmacology
MH  - Structure-Activity Relationship
MH  - Transcription Factors/drug effects/*physiology
MH  - Transcriptional Activation/*drug effects
MH  - Transfection
EDAT- 1995/12/22 00:00
MHDA- 1995/12/22 00:01
CRDT- 1995/12/22 00:00
PHST- 1995/12/22 00:00 [pubmed]
PHST- 1995/12/22 00:01 [medline]
PHST- 1995/12/22 00:00 [entrez]
AID - S0021-9258(17)31198-5 [pii]
AID - 10.1074/jbc.270.51.30765 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Dec 22;270(51):30765-72. doi: 10.1074/jbc.270.51.30765.