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I M Verma

Publications and source records attributed to I M Verma.

260 records · Page 15Linked to original sources
PubMedDate not supplied

Tissue and cell type-specific expression of two human c-onc genes.

Cellular genes containing nucleotide sequences homologous to retroviral oncogenes (v-onc) have been identified in the genomes of a variety of species of both the vertebrate and invertebrate phyla. Expression of such genes, termed c-onc genes, has been shown to be tissue-specific in chickens and mice and to be modulated during murine development and differentiation of human haematopoietic cells. We report here that the level of the c-fos gene transcripts is 100-fold greater in human term fetal membranes than in other normal human tissues and cells. These levels of c-fos expression in human amniotic and chorionic cells are close to the level of v-fos expression that results in the induction of osteosarcomas in mice and transformation of fibroblasts in vitro. This observation suggests that the induction of neoplastic transformation by the FBJ murine osteosarcoma virus may require the expression of the fos gene product at high levels in an inappropriate cell type. In contrast, the human c-fms gene is expressed at high levels specifically in term placenta and trophoblastic cells. The tissue and cell type-specific patterns of c-fos and c-fms expression suggest that the physiological function of the c-fos and c-fms encoded proteins may be associated with those embryo-derived cells whose primary functions are protection and nourishment of the human fetus.

Adult↗
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From c-fos to v-fos.

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Gene Expression Regulation↗
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Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus.

A role for proto-oncogenes in the regulation and modulation of cell proliferation has been suggested by the findings that the B-chain of platelet-derived growth factor (PDGF) is encoded by the proto-oncogene sis and that the erb-B oncogene product is a truncated form of the epidermal growth factor (EGF) receptor. Furthermore, the product of the proto-oncogene fms (c-fms) may be related or identical to the receptor for macrophage colony-stimulating factor (CSF-1). v-fms is the transforming gene of the McDonough strain of feline sarcoma virus (SM-FeSV) and belongs to the family of src-related oncogenes which have tyrosine-specific kinase activity. Furthermore, nucleotide sequence analysis of the v-fms gene product revealed topological properties of a cell-surface receptor protein. To elucidate the features involved in the conversion of a normal cell-surface receptor gene into an oncogenic one, we have now determined the complete nucleotide sequence of a human c-fms complementary DNA. The 972-amino-acid c-fms protein has an extracellular domain, a membrane-spanning region, and a cytoplasmic tyrosine protein kinase domain. Comparison of the feline v-fms and human c-fms sequences reveals that the proteins share extensive homology but have different carboxyl termini.

Amino Acid Sequence↗
PubMedDate not supplied

Modulation of c-fos gene transcription by negative and positive cellular factors.

Regulation of transcription in eukaryotes is mediated by the specific interaction between cellular factors and promoter sequences. Cis-acting DNA sequences, frequently located upstream of the TATA box, have been implicated in modulating the expression of many genes. We are interested in the transcriptional regulation of proto-oncogenes because they may have a pivotal function in cell growth and differentiation. Expression of the proto-oncogene c-fos is induced in response to a variety of growth factors and differentiation-specific agents. The viral cognate of the c-fos gene is the resident transforming gene of FBJ-murine osteosarcoma virus which causes bone tumours in vivo and cellular transformation in vitro. We report here that transcription of the human c-fos gene is modulated by negatively and positively acting cellular factors.

Animals↗