The Role of Environmental Carcinogens, Viruses, and Genetic

Cdk9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a ad T2b) and cyclin K. The Cdk9/cyclin T complexes appear to be involved in regulating several physiological processes. Cdk9/cyclin T1 belongs to the P-TEFb complex, and is responsible for the phosphorylation of the carboxyl-terminal domain (CTD) of the RNA Polymerase II, thus promoting general elongation. Cdk9 has also been described as the kinase of the TAK complex, which is homologous to the P-TEFb complex and involved in HIV replication. Cdk9 also appears to be involved in the differentiation program of several cell types, such as muscle cells, monocytes and neurons, suggesting that it may have a function in controlling specific differentiative pathways. In addition, Cdk9 seems to have an anti-apoptotic function in monocytes, that may be related to its control over differentiation of monocytes. This data suggests the involvement of Cdk9 in several physiological processes in the cell, the deregulation of which may be related to the genesis of transforming events, that may in turn lead to the onset of cancer. In addition, since the complex Cdk9/cyclin T1 is able to bind to the HIV-1 product Tat, the study of the functions of Cdk9/cyclin T may be of interest in understanding the basal mechanisms that regulate HIV replication.

[1]  S. Jhanwar,et al.  SV40 infection induces telomerase activity in human mesothelial cells , 2002, Oncogene.

[2]  D. Yates,et al.  Malignant mesothelioma in south east England: clinicopathological experience of 272 cases. , 1997, Thorax.

[3]  C. Cicala,et al.  The Role of Small t Antigen in SV40 Oncogenesis , 1991 .

[4]  G. Berry,et al.  The Effects of the Inhalation of Asbestos in Rats , 1974, British Journal of Cancer.

[5]  H. Pass,et al.  Simian virus 40, poliovaccines and human tumors: a review of recent developments , 1997, Oncogene.

[6]  S. Steinberg,et al.  Simian virus-40 large-T antigen binds p53 in human mesotheliomas , 1997, Nature Medicine.

[7]  V. Roggli,et al.  Pathology of Asbestos-Associated Diseases , 2004, Springer New York.

[8]  H. Pass,et al.  The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas , 1997, Nature Medicine.

[9]  J. Lokich,et al.  Familial mesothelioma after intense asbestos exposure at home. , 1978, JAMA.

[10]  H. Weill,et al.  Asbestos exposure--quantitative assessment of risk. , 1986, The American review of respiratory disease.

[11]  A. Smith,et al.  Chrysotile asbestos is the main cause of pleural mesothelioma. , 1996, American journal of industrial medicine.

[12]  H. Pass,et al.  Simian virus 40-like DNA sequences in human pleural mesothelioma. , 1994, Oncogene.

[13]  J. Butel,et al.  Cell and molecular biology of simian virus 40: implications for human infections and disease. , 1999, Journal of the National Cancer Institute.

[14]  J. Testa,et al.  SV40 and cell cycle perturbations in malignant mesothelioma. , 2001, Seminars in cancer biology.

[15]  R. Robledo,et al.  Cellular and molecular mechanisms of asbestos‐induced fibrosis , 1999, Journal of cellular physiology.

[16]  W. E. Smith,et al.  The Intrapleural Route as a Means for Estimating Carcinogenicity , 1974 .

[17]  B. Lanphear,et al.  Latent period for malignant mesothelioma of occupational origin. , 1992, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[18]  S. Weitzman,et al.  Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. , 1996, Cancer investigation.

[19]  A. Churg,et al.  Mechanisms in the pathogenesis of asbestosis and silicosis. , 1998, American journal of respiratory and critical care medicine.

[20]  C. L. Sanders,et al.  Induction of mesotheliomas and sarcomas from "hot spots" of 239 PuO 2 activity. , 1972, Health physics.

[21]  A. Seaton,et al.  Asbestos: scientific developments and implications for public policy. , 1990, Science.

[22]  C. Cicala,et al.  SV40 induces mesotheliomas in hamsters. , 1993, The American journal of pathology.

[23]  G. Berry,et al.  Mesotheliomata in Rats after Inoculation with Asbestos and Other Materials , 1973, British Journal of Cancer.

[24]  G. Sluis-Cremer Asbestos Disease at Low Exposures after Long Residence Times , 1991, Annals of the New York Academy of Sciences.

[25]  N. Vianna,et al.  NON-OCCUPATIONAL EXPOSURE TO ASBESTOS AND MALIGNANT MESOTHELIOMA IN FEMALES , 1978, The Lancet.

[26]  J. Testa,et al.  Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey , 2001, The Lancet.

[27]  M. Stanton,et al.  Mechanisms of mesothelioma induction with asbestos and fibrous glass. , 1972, Journal of the National Cancer Institute.

[28]  B. Price Analysis of current trends in United States mesothelioma incidence. , 1997, American journal of epidemiology.

[29]  P. Landrigan,et al.  The third wave of asbestos disease: exposure to asbestos in place. Public health control. Introduction. , 1991, Annals of the New York Academy of Sciences.