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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes.
Mol Cell Biol 1991 Dec
PMID:The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells. 194 89

The proto-oncogenes are thought to play important roles in the regulation of cellular growth and differentiation. In order to evaluate the role of proto-oncogenes in the regulation of growth of bronchial epithelial cells, we studied steady-state levels of fos, jun, and myc transcripts in response to fetal calf serum, bovine pituitary extract, and insulin. Extensively quiescent populations of bovine bronchial epithelial cells in growth factor-free medium were stimulated to divide by each of these three additives. We observed rapid but transient increases of fos, jun, and myc expression in association with such growth stimulation. There were no changes in tubulin mRNA levels over the same time periods. Other "growth factors" (epidermal growth factor, hydrocortisone, epinephrine, triiodothyronine, and transferrin) were also studied and did not affect either cell growth or expression of fos, jun, or myc. We further examined the effect of transforming growth factor-beta1 (TGF-beta1) on the above stimulatory effects. TGF-beta1 consistently inhibited the growth induced by fetal calf serum, bovine pituitary extract, or insulin and, interestingly, reduced proto-oncogene myc mRNA level without altering that of fos and jun. In conclusion, proto-oncogenes fos, jun, and myc appear to play a role in the regulation of growth response in bovine bronchial epithelial cells. It is also possible that TGF-beta1 exerts its growth inhibitory effect, at least in part, through the processes that involve the regulation of proto-oncogene myc transcription in these cells.
Am J Respir Cell Mol Biol 1991 Dec
PMID:Regulation of bovine bronchial epithelial cell proliferation and proto-oncogene expression by growth factors. 195 82

We have studied the mechanism by which 17 beta-oestradiol (E2) stimulates breast cancer proliferation using the MCF7 cell line as a model system. We provide evidence that E2 directly stimulates cellular proliferation by inducing, like many growth factors, the c-fos proto-oncogene. E2 by itself, however, is poorly mitogenic and it does not induce genes from the jun family, whose gene products are necessary for heterodimerization with the c-fos encoded protein (Fos), leading to an important step in growth factor signalling pathways, stimulation of the 12-O-tetradecanoyl-phorbol-13-acetate responsive element (TRE)-dependent transcriptional activity. In combination with insulin-like growth factors (IGFs), efficient inducers of c-jun in breast cancer cells, E2 synergistically stimulates TRE-activity and proliferation. This direct stimulation by E2 of growth factor signalling pathways suggest that E2 can directly induce proliferation, independent from autocrine growth factors.
J Steroid Biochem Mol Biol 1991
PMID:Oestrogen directly stimulates growth factor signal transduction pathways in human breast cancer cells. 195 24

The transforming gene product of avian erythroblastosis virus, v-erbB, is derived from the epidermal growth factor (EGF) receptor but has lost its extracellular ligand-binding domain and was mutated in its cytoplasmic portion, which is thought to be responsible for biological signal generation. We have repaired the deletion of extracellular EGF-binding sequences and investigated the functional consequences of cytoplasmic erbB mutations. Within the resulting EGF receptors, the autophosphorylation activities of the cytoplasmic domains of v-erbB-H and v-erbB-ES4 were fully ligand dependent in intact cells. However, the mitogenic and transforming signaling activities of an EGF receptor carrying v-erbB-ES4 (but not v-erbB-H) cytoplasmic sequences remained ligand independent, whereas those of a receptor with a v-erbB-H cytoplasmic domain were regulated by EGF or transforming growth factor alpha. Thus, structural alterations in the cytoplasmic domain of growth factor receptor tyrosine kinases may induce constitutive signaling activity without autophosphorylation. These findings provide new insight into the mechanism of receptor-mediated signal transduction and suggest a novel alternative for subversion of cellular control mechanisms and proto-oncogene activation.
Mol Cell Biol 1990 Jun
PMID:Epidermal growth factor receptor cytoplasmic domain mutations trigger ligand-independent transformation. 197 19

Forty-nine primary breast tumors were analyzed for the expression of the somatostatin receptor (SSR) and genetic changes in the RB tumor suppressor gene. Twenty-four tumor samples were shown to contain receptors for somatostatin and in eight of these SSR-positive tumors we observed a mutation in the RB gene. However, since also in the group of SSR-negative tumors in eight of the 25 cases an alteration of the RB gene was observed, loss of this tumor suppressor gene is not specific for the SSR-positive subgroup of breast tumors. A similar, equal distribution between SSR-positive and SSR-negative breast tumors was observed for the six tumor samples which showed amplification of the neu proto-oncogene.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Genetic changes in somatostatin receptor positive breast tumors. 198 Oct 16

The proto-oncogene c-myb, whose expression is usually limited to cells of the hematopoietic lineages, can be expressed in fibroblasts if placed under the control of a constitutive promoter, such as the simian virus SV40 early promoter. 3T3 cells carrying a constitutively expressed human c-myb were found to grow in 1% serum or in a serum-free, platelet-derived growth factor-supplemented medium, whereas the parent cell line, BALB/c 3T3, needed insulinlike growth factor 1 (IGF-1) in addition to platelet-derived growth factor for growth. myb-carrying cells, however, could not grow in platelet-poor plasma. In fibroblasts, therefore, a constitutively expressed c-myb can abrogate the requirement for platelet-poor plasma or IGF-1. When 3T3 cells constitutively expressed both c-myc and c-myb, they could grow in serum-free medium without added growth factors. The ability of c-myb to abrogate in fibroblasts the IGF-1 requirement seems to be due to its ability to induce overexpression of IGF-1, as indicated by an increase in steady-state levels of IGF-1 mRNA. These results have some important implications; for instance, they suggest a commonality of pathways for entry into S phase in different cell types and the possibility of a myb-like or myb-equivalent gene product of critical importance for entry of fibroblasts into S phase.
Mol Cell Biol 1991 Feb
PMID:Constitutively expressed c-myb abrogates the requirement for insulinlike growth factor 1 in 3T3 fibroblasts. 199 Feb 79

Neuroectodermal tumors of childhood provide a unique opportunity to examine the role of genes potentially regulating neuronal growth and differentiation because many cell lines derived from these tumors are composed of at least two distinct morphologic cell types. These types display variant phenotypic characteristics and spontaneously interconvert, or transdifferentiate, in vitro. The factors that regulate transdifferentiation are unknown. Application of antisense approaches to the transdifferentiation process has allowed us to explore the precise role that N-myc may play in regulating developing systems. We now report construction of an episomally replicating expression vector designed to generate RNA antisense to part of the human N-myc gene. Such a vector is able to specifically inhibit N-myc expression in cell lines carrying both normal and amplified N-myc alleles. Inhibition of N-myc expression blocks transdifferentiation in these lines, with accumulation of cells of an intermediate phenotype. A concomitant decrease in growth rate but not loss of tumorigenicity was observed in the N-myc nonamplified cell line CHP-100. Vector-generated antisense RNA should allow identification of genes specifically regulated by the proto-oncogene N-myc.
Mol Cell Biol 1991 Mar
PMID:Episome-generated N-myc antisense RNA restricts the differentiation potential of primitive neuroectodermal cell lines. 199 98

The c-abl proto-oncogene encodes a cytoplasmic tyrosine kinase which is homologous to the src gene product in its kinase domain and in the upstream kinase regulatory domains SH2 (src homology region 2) and SH3 (src homology region 3). The murine v-abl oncogene product has lost the SH3 domain as a consequence of N-terminal fusion of gag sequences. Deletion of the SH3 domain is sufficient to render the murine c-abl proto-oncogene product transforming when myristylated N-terminal membrane localization sequences are also present. In contrast, the human BCR/ABL oncogene of the Philadelphia chromosome translocation has an intact SH3 domain and its product is not myristylated at the N terminus. To analyze the contribution of BCR-encoded sequences to BCR/ABL-mediated transformation, the effects of a series of deletions and substitutions were assessed in fibroblast and hematopoietic-cell transformation assays. BCR first-exon sequences specifically potentiate transformation and tyrosine kinase activation when they are fused to the second exon of otherwise intact c-ABL. This suggests that BCR-encoded sequences specifically interfere with negative regulation of the ABL-encoded tyrosine kinase, which would represent a novel mechanism for the activation of nonreceptor tyrosine kinase-encoding proto-oncogenes.
Mol Cell Biol 1991 Apr
PMID:BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias. 200 81

Almost 30% of patients with T-cell acute lymphoblastic leukemia (T-ALL) bear structural alterations of tal-1, a presumptive proto-oncogene that encodes sequences homologous to the helix-loop-helix (HLH) DNA-binding and dimerization domain. Analysis of the tal-1 gene product reveals that its HLH domain mediates protein-protein interactions with either of the ubiquitously expressed HLH proteins E47 and E12. The resultant tal-1/E47 and tal-1/E12 heterodimers specifically recognize the E-box DNA sequence motif found in eucaryotic transcriptional enhancers. Hence, the tal-1 protein shares biochemical properties with other tissue-specific HLH proteins that control cell type determination during myogenesis (e.g., MyoD1) and neurogenesis (e.g., achaete-scute). The data suggest that HLH heterodimers involving tal-1 may function in vivo as transcriptional regulatory factors that influence cell type determination during hematopoietic development.
Mol Cell Biol 1991 Jun
PMID:Enhancer-binding activity of the tal-1 oncoprotein in association with the E47/E12 helix-loop-helix proteins. 203 15

A series of v-rasH effector domain mutants were analyzed for their ability to transform rat 2 cells at either low or high temperatures. Three mutants were found to be significantly temperature sensitive: Ile-36 changed to Leu, Ser-39 changed to Cys (S39C), and Arg-41 changed to Leu. Of these, the codon 39 mutant (S39C) showed the greatest degree of temperature sensitivity. When the same mutation was analyzed in the proto-oncogene form of ras(c-rasH), this gene was also found to be temperature sensitive for transformation. Biochemical analysis of the proteins encoded by v-rasH(S39C) and c-rasH(S39C) demonstrated that the encoded p21ras proteins were stable and bound guanine nucleotides in vivo at permissive and nonpermissive temperatures. On the basis of these findings, it is likely that the temperature-sensitive phenotype results from an inability of the mutant (S39C) p21ras to interact properly with the ras target effector molecule(s) at the nonpermissive temperature. We therefore analyzed the interaction between the c-rasH(S39C) protein and the potential target molecules GTPase-activating protein (GAP) and the GAP-related domain of NF-1, on the basis of stimulation of the mutant p21ras GTPase activity by these molecules in vitro. Assays conducted across a range of temperatures revealed no temperature sensitivity for stimulation of the mutant protein, compared with that of authentic c-rasH protein. We conclude that for this mutant, there is a dissociation between the stimulation of p21ras GTPase activity by GAP and the GAP-related domain NF-1 and their potential target function. Our results are also consistent with the existence of a distinct, as-yet-unidentified effector for mammalian ras proteins.
Mol Cell Biol 1991 Jun
PMID:A ras effector domain mutant which is temperature sensitive for cellular transformation: interactions with GTPase-activating protein and NF-1. 203 22


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