Receptor-Ck controls the expression of Bcl-2 and cyclin d genes.
By making use of receptor-Ck positive lymphocytes (from normal human subjects) as well as receptor-Ck negative lymphocytes (from untreated chronic myeloid leukemic (CML) patients) as cellular models, we were able to show that receptor-Ck-dependent signalling is involved in the regulation of genes coding for Bcl-2 and cyclin D. Further, experiments directed to resolve the mechanism by which this receptor regulates these genes revealed that receptor-Ck, upon activation by cholesterol, initiates the cleavage of a 125 kDa cytoplasmic protein leading to the generation of a 47 kDa factor having specific affinity for genomic sterol regulatory element (SRE)/SRE-like sequence present in the promoter region of genes coding for Bcl-2 and cyclin D. Based upon these observations, we propose that the inability of leukemic cells to express receptor-Ck is responsible for the deregulated over-expression of genes coding for Bcl-2 and cyclin D and this phenomenon may be of importance in understanding leukemic haematopoiesis.
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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D001483:Base Sequence; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2; D006801:Humans; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D018110:Receptors, Lipoprotein / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D056741:Cyclin D; D016213:Cyclins; D009838:Oligodeoxyribonucleotides; D018110:Receptors, Lipoprotein; C113493:receptor-Ck