The oligomerization chain reaction (OCR) strategy is a recently described technique for inactivation of target proteins that function as homoassociate complexes. This novel strategy is based on the fusion of self-associating coiled-coil (CC) domain of the nuclear factor promyelocytic leukemia (PML) to target proteins. Here, we present the successful application of the OCR strategy for inactivation of the heterodimeric Cdk9/cyclin T1 complex. Cyclin T1/Cdk9 (P-TEFb) complex is a positive regulator of gene transcription, whose function is underlined by the ability to phosphorylate the carboxyl-terminal domain (CTD) of the RNA polymerase II conferring productive transcript elongation. Fusion of the CC domain to Cdk9 leads to the formation of high molecular complexes to which the endogenous cyclin T1 is recruited. The CC-Cdk9 chimera effectively inhibits HIV-1 Tat activation, whose transcription activity is exquisitely dependent upon cyclin T1/Cdk9 function. Furthermore, expression of CC-Cdk9 protein inhibits cell proliferation, as shown by colony-formation assay. Collectively, our findings add further support to the OCR strategy for functional inactivation of hetero-associated factors such as the Cdk9/cyclin T1 complex, and highlight a putative function of Cdk9 in cell growth control.
Facilitation on abstract versions of the selection task can be produced by deontic content. Jackson and Griggs (1990) claimed that this finding depends on the presence of an explicit negative on the not-q card. We hypothesized that the removal of the explicit negative from this card made its deontic status ambiguous. Experiment 1 demonstrated that a not-q card presenting implicit negative is not selected, and most subjects select the only card that appears to be relevant from a deontic point of view (i.e. the p card). Experiments 2 and 3 showed that the presence of the explicit negative on the not-q card is not necessary for producing facilitation, provided that the form of this card makes it clear that the not-q individual is a potential violator. Experiment 4 showed that a high success rate can be obtained even with a not-q card presenting an implicit negative. The results are discussed in terms of the specificity of reasoning in the deontic domain.
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