Our results demonstrate that both pRb and one or more of the activator E2Fs are required for basal expression and xenobiotic induction of several members of the detoxification pathway. Active pRb controls cell proliferation by negatively regulating the activator E2Fs. Thus, ablation of pRb leads to E2F-dependent gene transcription and cell proliferation. We have recently shown that both pRb and the activator E2Fs are also required to establish repression of E2F-dependent transcription as progenitor cells exit the cell cycle and differentiate. Under these conditions other RB family members cannot compensate for pRb loss, suggesting that pRb-E2F1-3 complexes must first bind E2F-dependent promoters prior to the establishment of the permanent repressing complex, which consists of p130-E2F4. Furthermore, under some stress conditions such as DNA damage, pRb, and not p107 or p130, is involved in blocking the cell cycle. Perhaps tissues respond to chemo- or genotoxic stress by inducing pRb, which, in cooperation with the activator E2Fs,Cryptochlorogenic-acid blocks cell proliferation and induces the detoxification response. This model suggests that the loss of pRb function during tumorigenesis may have effects on the ability of tumor cells to metabolize and eliminate toxins or to properly metabolize anticancer drugs. Specifically, our model would predict that compounds rendered less toxic by the detoxification pathway would be more genotoxic in RBKO cells. In fact, RBKO liver cells are more susceptible to tumorigenesis after treatment with aflatoxin B1, a drug converted to less toxic products by P450 enzymes. Similarly, our model predicts that cancer treatment with drugs activated by the P450 pathway would not be as effective in RB null background. Consistent with this, RB deficiency is associated with recurrence of breast cancer following tamoxifen therapy. Thus, the RB status impinges on the response to cytotoxic and therapeutic agents used in cancer treatment, reviewed in. In agreement with this view, intestinal crypts lacking either pRb or E2F1-2-3 show increased DNA damage, perhaps due to a defect in the detoxification process caused by the absence of either regulator. A better understanding of the interactions between pRb, E2Fs and drug metabolizing enzymes could yield valuable insights to design more efficient cancer treatments as well as to help minimize adverse reactions to multiple pharmacological substances in genetically diverse patients. In biology, a stoma is a tiny pore, found in the epidermal tissues of leaves and stems, which is used for gas exchange. The pore is bordered by a pair of kidney-shaped parenchyma cells known as guard cells, which are responsible for regulating the pore aperture of the opening. Ambient carbon dioxide enters the plant leaves through these stomatal pores, where it is used in photosynthesis. Oxygen produced by Salannal photosynthesis in the spongy layer cells of the leaf interior exits through these same openings. In plant respiration the oxygen enters the plant through the stomata, too. Also, water vapor is released into the atmosphere through these pores in a process called transpiration. The plant SLAC1 is a slow anion channel in the membrane of stomatal guard cell, which controls the turgor pressure in the aperture-defining guard cells of plant stomata, thereby regulating the exchange of water vapour and photosynthetic gases in response to environmental signals such as drought, high levels of carbon dioxide, and bacterial invasion. Studies proved that SLAC1 is activated by phosphorylation from the OST1 kinase. OST1 activity is negatively regulated by the ABI1 phosphatase, which is in turn inhibited by the stomatal ABA receptors PYR and RCAR when in the ternary hormone–receptor–phosphatase complex. Thereby, ABA stimulates SLAC1 channel activity.