E2FBP1/hDril1 modulates cell growth through downregulation of promyelocytic leukemia bodies.
Promyelocytic leukemia nuclear bodies (PML-NBs) comprise multiple regulatory factors and play crucial roles in the maintenance of cellular integrity, while unregulated activation of PML-NBs induces death and premature senescence. Hence, the function of PML-NBs must be directed properly; however, the mechanism that regulates PML-NBs remains unclear. In this paper, we show that PML-NBs are disintegrated by an AT-rich interaction domain family protein E2FBP1/hDril1 through specific desumoylation of promyelocytic leukemia protein (PML) in vivo and in vitro. RNA interference-mediated downregulation of E2FBP1/hDril1 results in hyperplasis of PML-NBs and consequent commitment to PML-dependent premature senescence. Thus, the function of E2FBP1/hDril1 is required for maintenance of survival potential of the cells. Our data suggest a novel mechanism to govern cellular integrity through the modulation of nuclear depots.
Fukuyo
Y
Y
Department of Molecular Cellular Oncology and Microbiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Mogi
K
K
Tsunematsu
Y
Y
Nakajima
T
T
D015153:Blotting, Western; D002455:Cell Division; D022003:Cell Nucleus Structures / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004926:Escherichia coli / Q000235:genetics; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007624:KB Cells; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism*; D009857:Oncogenes; D011233:Precipitin Tests; D034741:RNA, Small Interfering / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques
C490798:ARID3A protein, human; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D016650:Fluorescein-5-isothiocyanate