ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis

Kazutoshi Iijima, Hiroyuki Yamada, Masashi Miharu, Ken Ichi Imadome, Yoshitaka Miyagawa, Shingo Akimoto, Kenichiro Kobayashi, Hajime Okita, Atsuko Nakazawa, Shigeyoshi Fujiwara, Junichiro Fujimoto, Nobutaka Kiyokawa

研究成果: Article

7 引用 (Scopus)

抄録

We previously identified zinc finger (ZF) protein ZNF385B as a molecule specifically expressed in Burkitt's lymphoma (BL) among hematologic malignancies. Here, we investigated ZNF385B expression in healthy B cells in a variety of hematological tissues by RT-PCR and immunohistochemistry. ZNF385B expression was found to be limited to a subset of GC B cells, the healthy counterpart to BL B cells. To elucidate the function of ZNF385B in healthy B cells, we established a tetracycline-controlled protein-inducible system in B-cell lines and observed that ectopic expression of the longest transcript variant of ZNF385B, possessing four ZF domains, induced upregulation of PERP and FAS/CD95, a downstream target of p53, and activation of caspase, resulting in apoptosis induction. However, a ZNF385B deletion mutant with three ZF domains corresponding to shorter isoforms, did not induce upregulation; rather it inhibited apoptosis induced by CD20 cross-linking and BCR stimulation. The direct binding of ZNF385B with p53 has suggested the involvement of ZNF385B in B-cell apoptosis via modulation of p53 transactivation; our data indicate that ZNF385B characteristically expressed in GC B cells has both proapoptotic and antiapoptotic activities depending on the type of isoform and should be a novel player in GC B-cell selection.

元の言語English
ページ(範囲)3405-3415
ページ数11
ジャーナルEuropean Journal of Immunology
42
発行部数12
DOI
出版物ステータスPublished - 2012 12
外部発表Yes

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Germinal Center
B-Lymphocytes
Apoptosis
Zinc Fingers
Burkitt Lymphoma
Protein Isoforms
Up-Regulation
B-Lymphocyte Subsets
Hematologic Neoplasms
Caspases
Tetracycline
Transcriptional Activation
Proteins
Immunohistochemistry
Cell Line
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

これを引用

Iijima, K., Yamada, H., Miharu, M., Imadome, K. I., Miyagawa, Y., Akimoto, S., ... Kiyokawa, N. (2012). ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis. European Journal of Immunology, 42(12), 3405-3415. https://doi.org/10.1002/eji.201242530

ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis. / Iijima, Kazutoshi; Yamada, Hiroyuki; Miharu, Masashi; Imadome, Ken Ichi; Miyagawa, Yoshitaka; Akimoto, Shingo; Kobayashi, Kenichiro; Okita, Hajime; Nakazawa, Atsuko; Fujiwara, Shigeyoshi; Fujimoto, Junichiro; Kiyokawa, Nobutaka.

:: European Journal of Immunology, 巻 42, 番号 12, 12.2012, p. 3405-3415.

研究成果: Article

Iijima, K, Yamada, H, Miharu, M, Imadome, KI, Miyagawa, Y, Akimoto, S, Kobayashi, K, Okita, H, Nakazawa, A, Fujiwara, S, Fujimoto, J & Kiyokawa, N 2012, 'ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis', European Journal of Immunology, 巻. 42, 番号 12, pp. 3405-3415. https://doi.org/10.1002/eji.201242530
Iijima, Kazutoshi ; Yamada, Hiroyuki ; Miharu, Masashi ; Imadome, Ken Ichi ; Miyagawa, Yoshitaka ; Akimoto, Shingo ; Kobayashi, Kenichiro ; Okita, Hajime ; Nakazawa, Atsuko ; Fujiwara, Shigeyoshi ; Fujimoto, Junichiro ; Kiyokawa, Nobutaka. / ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis. :: European Journal of Immunology. 2012 ; 巻 42, 番号 12. pp. 3405-3415.
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abstract = "We previously identified zinc finger (ZF) protein ZNF385B as a molecule specifically expressed in Burkitt's lymphoma (BL) among hematologic malignancies. Here, we investigated ZNF385B expression in healthy B cells in a variety of hematological tissues by RT-PCR and immunohistochemistry. ZNF385B expression was found to be limited to a subset of GC B cells, the healthy counterpart to BL B cells. To elucidate the function of ZNF385B in healthy B cells, we established a tetracycline-controlled protein-inducible system in B-cell lines and observed that ectopic expression of the longest transcript variant of ZNF385B, possessing four ZF domains, induced upregulation of PERP and FAS/CD95, a downstream target of p53, and activation of caspase, resulting in apoptosis induction. However, a ZNF385B deletion mutant with three ZF domains corresponding to shorter isoforms, did not induce upregulation; rather it inhibited apoptosis induced by CD20 cross-linking and BCR stimulation. The direct binding of ZNF385B with p53 has suggested the involvement of ZNF385B in B-cell apoptosis via modulation of p53 transactivation; our data indicate that ZNF385B characteristically expressed in GC B cells has both proapoptotic and antiapoptotic activities depending on the type of isoform and should be a novel player in GC B-cell selection.",
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AU - Iijima, Kazutoshi

AU - Yamada, Hiroyuki

AU - Miharu, Masashi

AU - Imadome, Ken Ichi

AU - Miyagawa, Yoshitaka

AU - Akimoto, Shingo

AU - Kobayashi, Kenichiro

AU - Okita, Hajime

AU - Nakazawa, Atsuko

AU - Fujiwara, Shigeyoshi

AU - Fujimoto, Junichiro

AU - Kiyokawa, Nobutaka

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AB - We previously identified zinc finger (ZF) protein ZNF385B as a molecule specifically expressed in Burkitt's lymphoma (BL) among hematologic malignancies. Here, we investigated ZNF385B expression in healthy B cells in a variety of hematological tissues by RT-PCR and immunohistochemistry. ZNF385B expression was found to be limited to a subset of GC B cells, the healthy counterpart to BL B cells. To elucidate the function of ZNF385B in healthy B cells, we established a tetracycline-controlled protein-inducible system in B-cell lines and observed that ectopic expression of the longest transcript variant of ZNF385B, possessing four ZF domains, induced upregulation of PERP and FAS/CD95, a downstream target of p53, and activation of caspase, resulting in apoptosis induction. However, a ZNF385B deletion mutant with three ZF domains corresponding to shorter isoforms, did not induce upregulation; rather it inhibited apoptosis induced by CD20 cross-linking and BCR stimulation. The direct binding of ZNF385B with p53 has suggested the involvement of ZNF385B in B-cell apoptosis via modulation of p53 transactivation; our data indicate that ZNF385B characteristically expressed in GC B cells has both proapoptotic and antiapoptotic activities depending on the type of isoform and should be a novel player in GC B-cell selection.

KW - Apoptosis

KW - B-cell development

KW - Cell survival

KW - DNA repair mechanisms

KW - Lymphoid organs

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