IRF-1 as a negative regulator of cell proliferation.
Numerous evidence has demonstrated the involvement in growth control of interferon (IFN) regulatory factor-1 (IRF-1), which shows tumor suppressor activity. IRF-1 is a well-studied member of the IRF transcription factors that reveals functional diversity in the regulation of cellular response by activating expression of a diverse set of target genes, depending on the cell type and on the specific stimuli. IRF-1 gene rearrangements may be a crucial point in the pathogenesis of some cancer types. Furthermore, different aspects of the tumor suppressor function of IRF-1 may be explained, at least in part, by the observations that IRF-1 is a regulator of cell cycle and apoptosis and that its inactivation accelerates cell transformation. Studies on gene knockout mice contributed greatly to the clarification of these multiple IRF-1 functions. We summarize our current knowledge of the antigrowth effect of IRF-1, focusing also on a more general involvement of IRF-1 in mediating negative regulation of cell growth induced by numerous cytokines and other biologic response modifiers.
Romeo
Giovanna
G
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy. romeo@iss.it
Fiorucci
Gianna
G
Chiantore
Maria V
MV
Percario
Zulema A
ZA
Vannucchi
Serena
S
Affabris
Elisabetta
E
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins