The nuclear orphan receptor TR4 promotes proliferation of myeloid progenitor cells.
Nuclear receptors represent key regulators in cell proliferation, differentiation, and development. Here we demonstrate that the nuclear orphan receptor TR4 is highly expressed in hematopoietic cells and tissues and have analyzed the impact of TR4 in this cell compartment. We show that TR4, when ectopically expressed in bone marrow cells via retrovirus vector, promotes proliferation of myeloid progenitor cells. Cells represent promyelocytes as judged by morphological features, expression of cell surface molecules, and specific markers like Mim-1 and CAAT/enhancer binding protein beta. We also demonstrate that the growth promoting activity of TR4 is not exclusively dependent on its association with DNA, because expression of a mutated TR4 version devoid of its DNA binding domain exhibits a similar proliferative potential as wild-type TR4. In conclusion, these data position the orphan receptor TR4 as an important regulator of myeloid progenitor cell proliferation and development.
Koritschoner
N P
NP
Max-Delbrück-Center for Molecular Medicine, D-13122 Berlin, Germany.
Madruga
J
J
Knespel
S
S
Blendinger
G
G
Anzinger
B
B
Otto
A
A
Zenke
M
M
Bartůnĕk
P
P
D000123:Acetyltransferases; D000818:Animals; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002455:Cell Division; D002645:Chickens; D004247:DNA / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D012190:Retroviridae / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D022782:CCAAT-Enhancer-Binding Protein-beta; C490515:NR2C2 protein, human; D009419:Nerve Tissue Proteins; C490514:Nr2c2 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus