title: Rb and nucleolin antagonize in controlling human CD34 gene expression.
abstract: Retinoblastoma protein (Rb) controls cell proliferation, differentiation, survival and gene expression and it has a central role in the signaling network that provides a cell cycle checkpoint in the G1 phase of the cell cycle. Studies in mice have shown that Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment and it acts as a critical regulator of hematopoietic stem and progenitor cells under stress. In human hematopoiesis, the CD34 protein is expressed on a subset of progenitor cells capable of self-renewal, multilineage differentiation, and hematopoietic reconstitution, and CD34 has a role in the differentiation of hematopoietic cells. Here we find that, in CD34-positive hematopoietic cells, Rb controls the human CD34 promoter region by antagonizing the CD34 promoter factor nucleolin to provide a mechanism that links expression of endogenous CD34 to cell cycle progression. Our study suggests a direct involvement of Rb in the transcriptional program of human CD34-positive hematopoietic stem/progenitor cells, thus providing further insights into the molecular network relevant to the features of these cells.
authors: Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Düsseldorf, Germany.
authors: Edgar
authors: E
authors: Grinstein
authors: Csaba
authors: C
authors: Mahotka
authors: Arndt
authors: A
authors: Borkhardt
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016193:G1 Phase; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase; D000097796:Nucleolin
chemical_list: D018952:Antigens, CD34; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; D000097796:Nucleolin