title: The role of MIZ-1 in MYC-dependent tumorigenesis.
abstract: A hallmark of MYC-transformed cells is their aberrant response to antimitogenic signals. Key examples include the inability of MYC-transformed cells to arrest proliferation in response to antimitogenic signals such as TGF-β or DNA damage and their inability to differentiate into adipocytes in response to hormonal stimuli. Given the plethora of antimitogenic signals to which a tumor cell is exposed, it is likely that the ability to confer resistance to these signals is central to the transforming properties of MYC in vivo. At the same time, the inability of MYC-transformed cells to halt cell-cycle progression on stress may establish a dependence on mutations that impair or disable apoptosis. We propose that the interaction of MYC with the zinc finger protein MIZ-1 mediates resistance to antimitogenic signals. In contrast to other interactions of MYC, there is currently little evidence that MIZ-1 associates with MYC in normal, unperturbed cells. The functional interaction of both proteins becomes apparent at oncogenic expression levels of MYC and association with MIZ-1 mediates both oncogenic functions of MYC as well as tumor-suppressive responses to oncogenic levels of MYC.
authors.affiliation: Comprehensive Cancer Center Mainfranken and Theodor Boveri Institute, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Katrin E
authors.initials: KE
authors.lastname: Wiese
authors.forename: Susanne
authors.initials: S
authors.lastname: Walz
authors.forename: Björn
authors.initials: B
authors.lastname: von Eyss
authors.forename: Elmar
authors.initials: E
authors.lastname: Wolf
authors.forename: Dimitris
authors.initials: D
authors.lastname: Athineos
authors.forename: Owen
authors.initials: O
authors.lastname: Sansom
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D017353:Gene Deletion; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D020721:Nervous System Autoimmune Disease, Experimental; D010212:Papilloma / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D012878:Skin Neoplasms / Q000235:genetics
chemical_list: D051741:Kruppel-Like Transcription Factors; D016271:Proto-Oncogene Proteins c-myc; C107961:ZBTB17 protein, human