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One of the mediators of interferon action is a latent endoribonuclease (ribonuclease L) that is activated by (2'-5')oligoadenylates. Among the homopolymers of the four common ribonucleotides, activated ribonuclease L degrades at an appreciable rate only polyuridylic acid. In two natural RNA's tested the most frequent ribonuclease L cleavages occur after UA, UG, and UU (A, adenine; U, uracil; and G, guanine) and much less frequent cleavages after CA and AC (C, cytosine).

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The interferons (IFNs) are cytokines with antiviral, antibacterial, antiprotozoal, immunomodulatory, and cell growth-regulatory functions. They exert these functions by controlling the expression of numerous genes encoding effector proteins (16,41,55,65). One set of effector proteins, including p202, p203, p204, and D3, is encoded by six or more structurally related and IFN-activatable murine genes at the q21-q23 region of chromosome 1 (gene 200 cluster) (13,36,42,48,59). Two homologous human proteins (myeloid cell nuclear differentiation antigen [MNDA] and IFI16) have also been described (7, 64). The proteins encoded by all these genes have homologous C-terminal 200-amino-acid segments (42).At least four of the proteins (p202, p204, MNDA, and IFI16) are nuclear (7,11,12,15,42). Upon treatment of cells with IFN, the induced p202 first appears in the cytoplasm, where it is attached to a fast-sedimenting subcellular component, and then accumulates in the nucleus after a delay (12). In metaphase cells, p202 appears to be associated with chromatin. Although p202 binds DNA in vitro, the cleavage of DNA in isolated nuclei does not result in the release of p202. This and other results suggest that the binding of p202 in the nucleus is at least in part due to protein-protein interactions.The proteins found to bind to p202 in vitro and in vivo include the retinoblastoma susceptibility protein pRb (10), which has a central role in controlling cell cycling (68). It is the hypophosphorylated, growth-inhibitory form of pRb that binds to p202. Overexpression of p202 in transfected cells slows down cell proliferation. The contribution of the interaction between p202 and pRb to the cell growth-inhibitory activity of p202 remains to be explored. However, the finding that p202 interacts with pRb prompted us to test whether p202 also interacts with other proteins controlling transcription. Here we describe studies concerning the effect of p202 on the NF-B p50 and p65 and the AP-1 c-Jun and c-Fos transcription factors. (5,56,57,60). The NF-B protein is a heterodimer consisting of two proteins, p50 (also designated NF-B 1 ) and p65 (also designated Rel A). p50 and p65 are members of the Rel/NF-B family of proteins. These proteins serve as inducible eukaryotic transcription factors that form various homo-and heterodimers. NF-B (i.e., the p50-p65 complex) is present in essentially all cells and is the most abundant of the Rel/NF-B family heterodimers. NF-B is retained in an inactive form in the cytoplasm as a consequence of the binding of particular proteins of the IB family (6, 24) (i.e., IB-␣ and IB-␤) (62). The activation of NF-B and its movement to the nucleus can be correlated with the proteolytic degradation of one or both of the IB proteins (8,46,49,60,62,63). This can be triggered by the phosphorylation of these proteins. The long list of agents activating NF-B includes various cytokines (e.g., interleukin-1 and tumor necrosis factor alpha), phorbol esters (e.g., phorbol myristate acetate [PMA] and tetradecanoyl phorbol ace...