@phdthesis{Staykov2012,
  author    = {Staykov, Nikola},
  title     = {The Role of the GABPα/β Transcription Factor In the Proliferation of NIH-3T3 Cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67655},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {SUMMARY GABP is a heterodymeric member of Ets-family transcription factors. It consists of two subunits - GABPa which contains DNA binding domain and GABPb, which provides transcriptional activation domain and nuclear localization signal. GABPa/b complex is essential for transcriptional activation of multiple lineage-restricted and housekeeping genes, several viral genes, and in some cases might function as transcriptional repressor. Large variety of data indicates involvement of GABP in the complex regulation of cell growth, specified by quiescence, stimulation/proliferation, apoptosis and senescence. Expression level of GABPa subunit is rapidly increased when resting cells enter S-phase, and GABPa/b complex is critical to promote the continuity of the cell cycle. Conditional inactivation of GABPa expression in mouse embryonic fibroblasts results in a complete block of proliferation and acquisition of senescence-like phenotype. However, the influence of GABP on the other cell growth determinant - the apoptosis - remains largely obscure. Therefore we aimed to investigate the influence of GABPa/b expression level on the cell growth in vitro. Using siRNA approach we achieved efficient but only transient down-regulation of GABPa expression which precluded further cell growth studies. Persistent increase of the expression of GABPb subunit only resulted in a positive effect on the cell growth speed. Simultaneous conditional overexpression of both GABPa and GABPb subunits though, strongly reduced the growth of the affected cell cultures in reversible and in expression level dependent manner. Interestingly, GABPa/b overexpressing cells did show neither cell cycle arrest nor massive induction of apoptosis. However, more detailed analyses revealed that dampened apoptotic processes were taking place in GABPa/b-overexpressing cells, starting with a prominent activation of caspase-12. Interestingly, activation of downstream effector caspases was rather suppressed explaining a weak increase of apoptotic cells in GABPa/b overexpressing cultures. This effect suggests that the activation of caspase-12 by elevated amounts of exogenous GABPa/b reflects the normal physiological mechanism of caspase-12 regulation.},
  subject      = {Proliferation},
  language  = {en}
}
@misc{SerflingAvotsKleinHesslingetal.2012,
  author    = {Serfling, Edgar and Avots, Andris and Klein-Hessling, Stefan and Rudolf, Ronald and Vaeth, Martin and Berberich-Siebelt, Friederike},
  title     = {NFATc1/alphaA: The other Face of NFAT Factors in Lymphocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75748},
  year      = {2012},
  abstract  = {In effector T and B cells immune receptor signals induce within minutes a rise of intracellular Ca++, the activation of the phosphatase calcineurin and the translocation of NFAT transcription factors from cytosol to nucleus. In addition to this first wave of NFAT activation, in a second step the occurrence of NFATc1/αA, a short isoform of NFATc1, is strongly induced. Upon primary stimulation of lymphocytes the induction of NFATc1/αA takes place during the G1 phase of cell cycle. Due to an auto-regulatory feedback circuit high levels of NFATc1/αA are kept constant during persistent immune receptor stimulation. Contrary to NFATc2 and further NFATc proteins which dampen lymphocyte proliferation, induce anergy and enhance activation induced cell death (AICD), NFATc1/αA supports antigenmediated proliferation and protects lymphocytes against rapid AICD. Whereas high concentrations of NFATc1/αA can also lead to apoptosis, in collaboration with NF-κB-inducing co-stimulatory signals they support the survival of mature lymphocytes in late phases after their activation. However, if dysregulated, NFATc1/αA appears to contribute to lymphoma genesis and - as we assume - to further disorders of the lymphoid system. While the molecular details of NFATc1/αA action and its contribution to lymphoid disorders have to be investigated, NFATc1/αA differs in its generation and function markedly from all the other NFAT proteins which are expressed in lymphoid cells. Therefore, it represents a prime target for causal therapies of immune disorders in future.},
  subject      = {Medizin},
  language  = {en}
}