Functional analysis of B-cell lymphoma specific zinc finger protein

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791211
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: IIJIMA Kazutoshi 独立行政法人国立成育医療研究センター, 小児血液・腫瘍研究部, 共同研究員 (30468508)
• Project Period (FY): 2011 – 2012
• Keywords: バーキットリンパ腫 / アポトーシス

Research Abstract

ZNF385B is a zinc finger protein that we previously identified as a molecule specifically expressed in BL using gene expression analyses. The biological significance of this protein has not been clarified at all. Therefore, we intended to elucidate diagnostic prospects and isoform-dependent functions of ZNF385B in B cells. Ectopic expression of ZNF385B IF-1 induced up-regulation of PERP (p53 apoptosis effector related to PMP-22) and activation of caspase-3 and -8, resulting in apoptosis induction, whereas IF-1/DEL did not. Furthermore, IF-1/DEL inhibited apoptosis induced by CD20 and BCR stimulation. Immunoprecipitation and yeast two-hybrid analysis indicated the direct binding of ZNF385B with p53. Since PERP is known to be a p53 transcriptional target, these results suggest the involvement of ZNF385B in B-cell apoptosis by modulating p53 transactivation. ZNF385B is considered to be involved in the regulation of death and survival that specifically occurs in GC B cells.

Research Products

• [Journal Article] ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis.
  • Author(s): Iijima K, Yamada H, Miharu M, Imadome K, Miyagawa Y, Akimoto S, Kobayashi K, Okita H, Nakazawa A, Fujiwara S, Fujimoto J, Kiyokawa N
  • Journal Title: Eur J Immunol Volume: Vol.42, No.12 Pages: 3405-3415
  • DOI: doi:10.1002/eji.201242530
  • Peer Reviewed
• [Presentation] ZNF385B is characteristically expressed in germinal center centroblast and induces apoptosis via PERP and FAS (2012)
  • Author(s): 飯島一智, 清河信敬
  • Organizer: 第41回日本免疫学会学術集会,
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-07
• [Presentation] Diagnostic prospects and isoform-dependent functions of Burkitt lymphoma specific protein ZNF385B, SIOP 2012 Congress (2012)
  • Author(s): Kazutoshi Iijima, Hiroyuki Yamada, Masashi Miharu, Atsuko Nakazawa, Junichiro Fujimoto, Kenichiro Kobayashi, Hajime Okita, Nobutaka Kiyokawa
  • Organizer: the 44th Congress of the International Society of Paediatric Oncology
  • Place of Presentation: London
  • Year and Date: 2012-10-07
• [Presentation] Isoform-dependent functions of Burkitt Lymphoma specific zinc-finger protein ZNF385B (2012)
  • Author(s): 飯島一智, 中澤温子, 藤本純一郎, 大喜多肇, 清河信敬
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] urkitt Lymphoma Specific Zinc Finger Protein ZNF385B Is Involved in Regulation of B Cell Apoptosis (2011)
  • Author(s): Kazutoshi Iijima, Hiroyuki Yamada, Masashi, Miharu, Atsuko Nakazawa, Junichiro Fujimoto, Kenichiro Kobayashi, Hajime Okita, and Nobutaka Kiyokawa
  • Organizer: 53rd American Society of Hematology Annual Meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2011-12-10
• [Presentation] バーキットリンパ腫特異的ジンクフィンガー蛋白によるB細胞のアポトーシス制御 (2011)
  • Author(s): 飯島一智, 清河信敬
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-27
• [Presentation] バーキットリンパ腫特異的分子ZNF385Bはp53を介してアポトーシスを制御する (2011)
  • Author(s): 飯島一智, 山田浩之, 三春晶嗣, 中澤温子, 藤本純一郎, 大喜多肇, 清河信敬
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] バーキットリンパ腫特異的分子ZNF385Bはp53に結合してアポトーシスを制御する (2011)
  • Author(s): 飯島一智, 中澤温子, 藤本純一郎, 大喜多肇, 清河信敬
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05