Negative regulation of the mammalian UV response by Myc through association with Miz-1

Mol Cell. 2002 Sep;10(3):509-21. doi: 10.1016/s1097-2765(02)00633-0.


The Myc oncoprotein represses initiator-dependent transcription through the POZ domain transcription factor Miz-1. We now show that transactivation by Miz-1 is negatively regulated by association with topoisomerase II binding protein (TopBP1); UV irradiation downregulates expression of TopBP1 and releases Miz-1. Miz-1 binds to the p21Cip1 core promoter in vivo and is required for upregulation of p21Cip1 upon UV irradiation. Using both c-myc(-/-) cells and a point mutant of Myc that is deficient in Miz-1 dependent repression, we show that Myc negatively regulates transcription of p21Cip1 upon UV irradiation and facilitates recovery from UV-induced cell cycle arrest through binding to Miz-1. Our data implicate Miz-1 in a pathway that regulates cell proliferation in response to UV irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • Cell Division / radiation effects
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA-Binding Proteins / metabolism*
  • Genes, Reporter
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / physiology
  • Keratinocytes / radiation effects
  • Kruppel-Like Transcription Factors
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors
  • Transcription, Genetic / radiation effects*
  • Transcriptional Activation*
  • Tumor Suppressor Proteins*
  • Two-Hybrid System Techniques
  • Ultraviolet Rays*


  • CDKN1A protein, human
  • CDKN2B protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • TOPBP1 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • ZBTB17 protein, human