title: Differential induction of the 200-family proteins in Daudi Burkitt's lymphoma cells by interferon-alpha.
abstract: Interferon (IFN)-inducible "effector" proteins mediate the biological activities of the IFNs. Therefore, the identification of the functional role(s) of IFN inducible proteins in IFN action is important to elucidate the molecular mechanisms by which IFNs inhibit cell growth. One family (the "200-family") of IFN-inducible proteins includes structurally related murine (p202a, p202b, p203, p204 and D3) and human (MNDA, IFI-16 and AIM2) proteins. However, their role in IFN action remains to be established. Here we report that IFN-alpha treatment of Daudi Burkitt's lymphoma cells resulted in differential induction of MNDA, IFI 16, and a p202-related protein (p202RP). Interestingly, IFN induction of p202RP preceded the induction of MNDA and IFI 16 proteins and the growth inhibition by IFN. Additionally, the induction of these proteins by IFN was accompanied by: (i) a transient increase in p21(WAF1/CIP1) levels; (ii) an increase in the functional form of pRb and p130; (iii) an inhibition of the sequence-specific DNA binding activity of E2F complexes; and (iv) a marked decrease in c-Myc levels. Our observations reported herein provide support to the hypothesis that IFN-inducible p202RP and MNDA proteins from the 200-family contribute to the growth inhibitory activities of the IFNs.
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Geng
authors.forename: D
authors.initials: D
authors.lastname: Choubey
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000737:chemistry; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000096:biosynthesis; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; C533431:Arid4a protein, mouse; C493956:CDKN1A protein, human; D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006131:Growth Inhibitors; C489664:Ifi16 protein, mouse; C092537:Ifi202b protein, mouse; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; C075373:MNDA protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; C498301:TP53BP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; C076700:IFI16 protein, human