title: PML-nuclear bodies are involved in cellular serum response.
abstract: BACKGROUND
  Serum stimulation leads to the activation of various signal transduction pathways in cells, and the resultant signals are integrated into the serum response factor (SRF)-dependent transcription of immediate-early genes such as c-fos.
  
  
  RESULTS
  To further characterize this response, we investigated the mechanism which controls serum response transcription in cultured human cells. Frequency of PML (promyelocytic leukaemia)-nuclear bodies (NBs) formation increases shortly after serum stimulation, probably facilitating the interaction of SRF and CBP acetyltransferase at the NBs. PML modulates SRF-mediated c-fos promoter activities upon addition of serum to cells or expression of constitutively active Rho family GTPases. We mapped the region in the SRF that interacts with PML to the C-terminal transactivation domain. An SRF mutant deleted of the transactivation domain neither co-localizes with CBP in NBs nor fulfills its transcriptional role. Under conditions of serum stimulation, the formation of NBs coincides with the immediate-early expression of the endogenous c-fos gene in fibroblasts and in all-trans retinoic acid-treated acute promyelocytic leukaemia NB4 cells.
  
  
  CONCLUSIONS
  These data provide an insight into the involvement of NBs in modulating the transcription of serum-induced immediate-early genes.
authors.affiliation: Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Minami
authors.forename: Masahide
authors.initials: M
authors.lastname: Tojo
authors.forename: Yoshiomi
authors.initials: Y
authors.lastname: Honda
authors.forename: Noriko
authors.initials: N
authors.lastname: Saitoh
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
mesh_terms: D001769:Blood / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011494:Protein Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D025521:Tumor Suppressor Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D011494:Protein Kinases; C405628:serum response factor kinase