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  • Hay, N  (4)
  • 1990-1994  (4)
  • Biology  (4)
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  • 1990-1994  (4)
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  • 1
    Online Resource
    Online Resource
    Informa UK Limited ; 1993
    In:  Molecular and Cellular Biology Vol. 13, No. 1 ( 1993-01), p. 383-390
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 13, No. 1 ( 1993-01), p. 383-390
    Abstract: The c-Myc oncoprotein, which is required for cellular proliferation, resembles in its structure a growing number of transcription factors. However, the mechanism of its action in vivo is not yet clear. The discovery of the specific cognate DNA-binding site for Myc and its specific heterodimerization partner, Max, enabled the use of direct experiments to elucidate how Myc functions in vivo and how this function is modulated by Max. Here we demonstrate that exogenously expressed Myc is capable of activating transcription in vivo through its specific DNA-binding site. Moreover, transcriptional activation by Myc is dependent on the basic region, the integrity of the helix-loop-helix and leucine zipper dimerization motifs located in the carboxy-terminal portion of the protein, and the regions in the amino terminus conserved among Myc family proteins. In contrast to Myc, exogenously expressed Max elicited transcriptional repression and blocked transcriptional activation by Myc through the same DNA-binding site. Our results suggest a functional antagonism between Myc and Max which is mediated by their relative levels in the cells. A model for the activity of Myc and Max in vivo is presented.
    Type of Medium: Online Resource
    ISSN: 0270-7306 , 1098-5549
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1993
    detail.hit.zdb_id: 1474919-1
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 1994
    In:  Genes & Development Vol. 8, No. 23 ( 1994-12-01), p. 2817-2830
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 8, No. 23 ( 1994-12-01), p. 2817-2830
    Abstract: Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 allele, we show that expression of wild-type p53 is required for susceptibility to Myc-mediated apoptosis. Although ectopic expression of wild-type p53 blocked cells in the G1 phase of the cell cycle, G1 arrest by isoleucine starvation, in a manner independent of p53, did not confer susceptibility to apoptosis. Thus, growth arrest per se is not sufficient to induce Myc-mediated apoptosis; instead, a property intrinsic to p53 is specifically required. Moreover, apoptosis did not require induction of p53 target proteins, including the cyclin-dependent kinase inhibitor p21waf1/cip1. Therefore, the role of p53 in apoptosis may be distinct from its role in cell cycle arrest.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1994
    detail.hit.zdb_id: 1467414-2
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1992
    In:  Proceedings of the National Academy of Sciences Vol. 89, No. 7 ( 1992-04), p. 3111-3115
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 89, No. 7 ( 1992-04), p. 3111-3115
    Abstract: The Max gene encodes a protein that interacts specifically with the Myc protein to form a heterodimer with high affinity for the specific cognate DNA binding site of Myc. Here we examine the expression of Max RNA in comparison to Myc RNA during cell growth and differentiation. Two species of RNA, a major 2.0- and a minor 1.7-kilobase species, hybridized specifically to a Max cDNA probe in all human and murine cell lines that were tested. Unlike Myc, the steady-state level of Max RNA is not significantly modulated with respect to proliferation or differentiation. Max RNA is expressed in quiescent BALB/c 3T3 cells and is modestly increased 3 h after addition of serum to the quiescent cells. In contrast to Myc RNA, Max RNA does not decline immediately upon induction of differentiation of HL60 cells by dimethyl sulfoxide, and only a modest decrease of Max RNA was observed 72 h after induction of differentiation. Unlike Myc RNA, Max RNA is relatively stable with a half-life of greater than 3 h and, therefore, does not exhibit the characteristic short half-life of RNAs encoded by most immediate early genes. The human Max gene was localized to chromosome 14, band q23. With respect to the recurring abnormalities in human tumors, this region of chromosome 14 is involved in deletions in B-cell chronic lymphocytic leukemia and malignant lymphomas and in the 12;14 translocation in uterine leiomyomas.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1992
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Informa UK Limited ; 1993
    In:  Molecular and Cellular Biology Vol. 13, No. 4 ( 1993-04), p. 2432-2440
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 13, No. 4 ( 1993-04), p. 2432-2440
    Abstract: The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto-oncogene bcl2, which has been shown to block apoptosis in other systems, with c-myc in serum-deprived Rat 1a fibroblasts. Here we report that ectopic expression of bcl2 specifically blocks apoptosis induced by constitutive c-myc expression. Constitutive c-myc expression in serum-deprived Rat 1a cells caused a 〉 15-fold increase in the number of dead cells, accompanied by DNA fragmentation. However, coexpression of bcl2 with c-myc in these cells led to a 10-fold increase in the number of live cells and a significant decrease in DNA fragmentation. Thus, Bcl-2 effectively inhibits Myc-induced apoptosis in serum-deprived Rat 1a fibroblasts without blocking entry into the cell cycle. These results imply that apoptosis serves as a protective mechanism to prevent tumorigenicity elicited by deregulated Myc expression. This protective mechanism is abrogated, however, by Bcl-2 and therefore may explain the synergism between Myc and Bcl-2 observed in certain tumor cells.
    Type of Medium: Online Resource
    ISSN: 0270-7306 , 1098-5549
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1993
    detail.hit.zdb_id: 1474919-1
    SSG: 12
    Location Call Number Limitation Availability
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