RRC ID 77511
Author Inagaki T, Suzuki S, Miyamoto T, Takeda T, Yamashita K, Komatsu A, Yamauchi K, Hashizume K.
Title The retinoic acid-responsive proline-rich protein is identified in promyeloleukemic HL-60 cells.
Journal J Biol Chem
Abstract To identify new genes that retinoic acid activates, we employed an mRNA differential display technique and screened for genes that are differentially expressed in promyeloleukemic HL-60 cells incubated in the presence of all-trans-retinoic acid (ATRA) compared with the absence of ATRA. We cloned the coding region of a retinoic acid-induced gene from a human thymus library, which was the mRNA encoding the 666-amino acid human homologue of mouse proline-rich protein 76. We have designated it RARP1 (retinoic acid response proline-rich protein 1). Transcription of an approximately 2.4-kbp mRNA occurred mainly in organs with immune functions, such as thymus, spleen, and peripheral leukocytes. Cycloheximide blocked the ATRA-induced expression. In megakaryocyte-like human erythroleukemia HEL cells, the amount of RARP1 mRNA was high, but it was low in human T-lymphoblastoid Jurkat cells. A specific antibody against RARP1 recognized a 110-kDa protein, which accumulates after incubation of HL-60 cells with ATRA. In immunohistochemical experiments, strong RARP1 staining was observed in the megakaryocytes of bone marrow and spleen, and heterogeneous stain was seen in thymus. Transcriptional studies showed that RARP1 expression impaired the transactivation through activator protein1 and serum response-element in all cell lines we checked, whereas it did not affect the transactivation through cAMP-response element in the same cell lines. Further analysis demonstrated that proline-rich regions of RARP1 are the functional regions regulated for suppression of activator protein1 transactivation. These data suggest that ATRA-inducible RARP1 selectively affects signal transduction and may contribute to myeloid and megakaryocytic differentiation.
Volume 278(51)
Pages 51685-92
Published 2003-12-19
DOI 10.1074/jbc.M308016200
PII S0021-9258(20)75435-9
PMID 14530287
MeSH Base Sequence Cell Differentiation Cloning, Molecular Gene Expression Profiling HL-60 Cells Hematopoietic System / metabolism Humans Immune System / metabolism Leukemia, Promyelocytic, Acute / pathology* Megakaryocytes / metabolism Molecular Sequence Data Peptides / analysis Peptides / drug effects* Peptides / physiology* Proline-Rich Protein Domains Protein Structure, Tertiary RNA, Messenger / analysis Signal Transduction Transcriptional Activation Tretinoin / pharmacology*
IF 4.238
Human and Animal Cells HL60(RCB0041)