RESUMO
Human cyclin A1 is a newly cloned, tissue-specific cyclin that is prominently expressed in normal testis. In this study, we showed that cyclin A1 was highly expressed in a subset of leukemia samples from patients. The highest frequency of cyclin A1 overexpression was observed in acute myelocytic leukemias, especially those that were at the promyelocyte (M3) and myeloblast (M2) stages of development. Cyclin A1 expression was also detected in normal CD34(+) progenitor cells. The expression of cyclin A1 increased when these cells were stimulated to undergo myeloid differentiation in vitro. Taken together, our observations suggest that cyclin A1 may have a role in hematopoiesis. High levels of cyclin A1 expression are especially associated with certain leukemias blocked at the myeloblast and promyelocyte stages of differentiation.
Assuntos
Ciclina A/genética , Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Leucemia/metabolismo , Antígenos CD34/análise , Northern Blotting , Diferenciação Celular , Ciclina A/análise , Ciclina A1 , Citometria de Fluxo , Imunofluorescência , Células-Tronco Hematopoéticas/imunologia , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Promielocítica Aguda/metabolismo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Proteínas Aviárias , Proteínas de Ligação a DNA/química , Proteínas Oncogênicas , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/metabolismo , Retroviridae/genética , Retroviridae/metabolismo , Proteínas Virais , Animais , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead , Genoma Viral , Sequências Hélice-Alça-Hélice , Humanos , Mamíferos , Proteínas Proto-Oncogênicas/genéticaRESUMO
The chicken winged helix proteins, CWH-1, CWH-2 and CWH-3, were isolated and identified by homology cloning using the winged helix sequence of the retroviral oncogene qin as a probe. The CWH proteins act as growth stimulators in chicken embryo fibroblasts and in this activity resemble the Qin protein. Qin is a transcriptional regulator that functions as a repressor, and its oncogenic potential is correlated with the ability to repress transcription. In this communication we show that CWH proteins are localized in the cell nucleus, recognize the Qin DNA binding site and also function as transcriptional repressors. The repression activity of CWH-3 was mapped to the region of amino acids 211 to 311, a domain that is homologous to the major repression domain of Qin.
Assuntos
Proteínas Aviárias , Proteínas de Ligação a DNA/fisiologia , Proteínas Repressoras/fisiologia , Fatores de Transcrição/fisiologia , Sítios de Ligação , DNA/metabolismoRESUMO
Winged helix transcription factors act as important regulators of embryonal development and tissue differentiation in vertebrates and invertebrates. Identification of the retroviral oncogene v-qin as a member of the winged helix family showed that these developmental regulators also have oncogenic potential. We used low-stringency hybridization of a chicken embryonic cDNA library to isolate cDNA clones coding for the three chicken winged helix (CWH) proteins, CWH-1, CWH-2, and CWH-3. The CWH genes are transcribed in a tissue-restricted pattern in adult and embryonic chicken tissues. The CWH proteins bind to conserved DNA binding sites for winged helix proteins in a sequence-specific manner. Expression of the CWH proteins from replication-competent retroviral RCAS vectors induces changes in morphology and growth pattern of chicken embryo fibroblasts. CWH-1 and CWH-3 also induce anchorage-independent growth in agar. Chicken embryo fibroblasts expressing the RCAS constructs release replication-competent viruses that are able to elicit the same cellular changes as the parental plasmid DNA. Our results suggest that winged helix transcription factors not only function as regulators of development and differentiation but also have the potential to stimulate abnormal cell proliferation.
