The nucleolus regulates hematopoietic cell differentiation

• Project/Area Number: 24770178
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Doshisha University
• Principal Investigator: KURODA Takao 同志社大学, 高等研究教育機構, 助教 (30620637)
• Project Period (FY): 2012 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 核小体 / リボソームRNA / 血球系細胞分化 / )核小体

Research Abstract

In this study, I have tried to address the role of the nucleolus in cellular differentiation. I found that rRNA transcription was downregulated during hematopoietic differentiation in both human leukemia cell line and mouse hematopoietic stem cells. In response to the inhibition of rRNA transcription, nucleolar protein MYBBP1A was translocated from the nucleolus to the nucleoplasm and interacted with c-Myc, which is one of the master regulator of hematopoietic differentiation. MYBBP1A attenuated transcriptional activity of c-Myc and promoted megakaryocytic differentiation. I also found that hematopoietic differentiation was sufficiently induced by specific suppression of rRNA transcription using actinomycin D or siRNA for TIF-IA. These results suggest that the downregulation of rRNA transcription accelerates cellular differentiation at least in hematopoietic cells.

Research Products

• [Journal Article] The nucleolar protein Myb-binding protein 1A (MYBBP1A) enhances p53 tetramerization and acetylation in response to nucleolar disruption. (2014)
  • Author(s): Ono W, Hayashi Y, Yokoyama W*, Kuroda T, Kishimoto H, Ito I, Kimura K, Akaogi K, Waku T, Yanagisawa J.
  • Journal Title: Journal of Biological Chemistry Volume: 289(8) Pages: 4928-4940
  • Peer Reviewed
• [Journal Article] The nucleolar protein Myb-binding protein 1A (MYBBP1A) enhances p53 tetramerization and acetylation in response to nucleolar disruption (2014)
  • Author(s): Ono W*, Hayashi Y*, Yokoyama W*, Kuroda T, Kishimoto H, Ito I, Kimura K, Akaogi K, Waku T, Yanagisawa J. (*: equal contribution)
  • Journal Title: Journal of Biological Chemistry Volume: 289(8) Pages: 4928-4940
  • Peer Reviewed
• [Journal Article] Nucleolar protein, Myb-binding protein 1A, specifically binds to nonacetylated p53 and efficiently promotes transcriptional activation. (2013)
  • Author(s): Ono W, Akaogi K, Waku T, Kuroda T, Yokoyama W, Hayashi Y, Kimura K, Kishimoto H, Yanagisawa J.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 434(3) Pages: 659-663
  • Peer Reviewed
• [Journal Article] Nucleolar protein, Myb-binding protein 1A, specifically binds to nonacetylated p53 and efficiently promotes transcriptional activation (2013)
  • Author(s): Ono W*, Akaogi K*, Waku T, Kuroda T, Yokoyama W, Hayashi Y, Kimura K, Kishimoto H, Yanagisawa J. (*: equal contribution)
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 434(3) Pages: 659-663
  • Peer Reviewed