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The SA mutant retained the ability to interact with the endogenous COP1. Upon stimulation with UV, the slower migrating form of FIP200 decreased and the faster migrating form increased in control cells. Overexpression of wild type COP1 reduced the level of faster migrating form at time 0 and blocked its induction by UV stimulation, whereas overex pression of SA mutant did not affect the band shift of FIP200 upon UV stimulation. FIP200 was identified as a tumor suppressor. If COP1 negatively regulates FIP200, one might expect that COP1 act as an oncogene. In addition, COP1 responds to UV stimulation and becomes a substrate of ATM/ ATR kinases. We, therefore, tested whether the overexpression of COP1 facilitates cellular transform ation in response to UV irradiation. We treated NIH3T3 mouse fibroblasts expressing COP1 with UV, let them recover for passaging, and subcutaneously injected them into NOD SCID mice. Ectopic expression of the COP1 protein itself was not tumorigenic because no trace of cells was detected 2 months after injection. However, after treatment with UV and successive pas sages in a recovery culture, cells ectopically expressing COP1 formed a tumor of significant size in mice. Im portantly, cells transfected with SA mutant of COP1, which did not interact with FIP200, failed to form tumors even after UV stimulation, suggesting that COP1 requires interaction with FIP200 to exhibit its oncogenic properties. We currently do not know the physiological significance of the impact of COP1 overex pression on autophagy. However, considering the differ ential effect on the expression of the components of the FIP200 complex and the FIP200 subtypes and that tumorigenic function of COP1 requires interaction with FIP200, it is feasible to say that COP1 may regulate bio logical activities associated with FIP200 in a certain occasion. Discussion As distinct from its plant counterpart, mammalian COP1 is involved in many biological occasions. Multi functionality of COP1 partly stems from its variety of substrates and various adaptor or accessory proteins to interact with. Although several proteins have been identified as the target of COP1, it is rea sonable to speculate that more substrates and down stream pathways are yet to be found. Our findings imply that autophagy may situate downstream of the signaling pathway mediated by COP1which may partly explain the multifunction of COP1 because autophagy is reported to be involved in many biological occasions. By yeast two hybrid screening, we identified C terminal polypeptide of FIP200 as the interactor of COP1, and raised antibody against this portion of the protein.