Phosphorylation of BCL6 protein

BCL6 蛋白的磷酸化

• 批准号: 10670194
• 负责人: MORIYAMA Masatsugu
• 金额: $ 2.05万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670194/
• 关键词: BCL6; Chromosomal translocation; phosphorylation; transcription factor; malignant lymphoma; BCL-6; MAP kindse; アポトーシス; BCL-2

BCL-6 gene alterations have been observed in 27-45% of diffuse large B-cell lymphomas (DLBs) with chromosomal translocations at 3q27. The deregulated expression of normal BCL-6 protein caused by this chromosomal translocation is believed to be responsible for lymphomagenesis. Recently, we demonstrated that BCL-6 is expressed at high levels in germinal center B-cells as a 92-98 kDa nuclear protein in a constitutively phosphorylated form. In this study, we show that BCL-6 is phosphorylated by mitogen-activated protein kinase(MAPK) in vitro at the sites phosphorylated in vivo. These numerous phosphorylation sites were found to be located in its serine- and proline-clustered (SPC) region (amino acids-250-483). BCL-6 phosphorylation significantly increased in Ramos cells following stimulation with 12-o-tetradecanoylphorbol-13-acetate (TPA) or BCL-6- and erk1-transfected COS-7 cells stimulated with epidermal growth factor (EGF), and the increase of phosphorylation was inhibited by MEK1 inhibitor, PD98059. Furthermore, we observed that BCL-6 was associated with MAPK in vivo and its SPC region was important for this association. These results suggest that the functions of BCL-6 are regulated by phosphorylation mediated by the MAPK signaling pathway.

在染色体易位位于3q27的弥漫性大B细胞淋巴瘤(DLB)中，已观察到27-45%的BCL-6基因改变。这种染色体易位引起的正常bcl6蛋白表达的失调被认为是导致淋巴肿大的原因。最近，我们证明了bcl6在生发中心B细胞中高水平表达，是一种92-98 kDa的核蛋白，以一种组成性的磷酸化形式存在。在这项研究中，我们发现bcl-6在体外被丝裂原活化蛋白激酶(MAPK)在体内磷酸化的位置上磷酸化。这些大量的磷酸化位点被发现位于其丝氨酸和脯氨酸聚集区(SPC)(氨基酸-250-483)。经12-O-十四酰佛波醇-13-乙酸酯(TPA)或转BCL-6和ERK1基因的COS-7细胞用表皮生长因子(EGF)刺激后，Ramos细胞中bcl6的磷酸化水平显著增加，而MEK1抑制剂PD98059可抑制该作用。此外，我们观察到BCL-6在体内与MAPK相关，其SPC区域对这种联系是重要的。这些结果表明，bcl6的功能受MAPK信号通路介导的磷酸化调节。

项目成果

Yoshida,S.: "Identification of heterologous translocation partner genes fused to the BCL6 gene in diffuse large B-cell lymphomas: 5-RACE and LA-PCR analyses of biopsy samples"Oncogene. 18. 7994-7999 (1999)

Yoshida,S.：“弥漫性大 B 细胞淋巴瘤中与 BCL6 基因融合的异源易位伴侣基因的鉴定：活检样本的 5-RACE 和 LA-PCR 分析”Oncogene。

Nakamura, T.: "The retroviral integration site, Evi-9, encodes a novel zinc finger protein which interacts with BCL-6"Mol. Cel. Biol.. (in press).

Nakamura, T.：“逆转录病毒整合位点 Evi-9 编码一种与 BCL-6 相互作用的新型锌指蛋白”Mol。

Moriyama, M.: "BCL-6 is phosphorylated at multiple sites in its serine- and proline-clustered region by mitogen -activated protein kinase(MAPK) in vivo"Oncogene. 14. 2465-2474 (1997)

Moriyama, M.：“BCL-6 在体内的丝氨酸和脯氨酸簇区域的多个位点被丝裂原激活蛋白激酶 (MAPK) 磷酸化”癌基因。

T.Yamochi: "Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death dccompanied by down-regulation of BCL-2 and BCL-XL" Oncogene. 18. 487-494 (1999)

T.Yamochi：“CV-1 细胞中腺病毒介导的 BCL-6 高表达可诱导细胞凋亡，并伴有 BCL-2 和 BCL-XL 的下调”Oncogene。

Nakamura,T.: "The retroviral integration site,Evi-9,encodes a novel zinc finger protein which interacts with BCL-6"Mol.Cel.Biol.. (in press).

Nakamura,T.：“逆转录病毒整合位点 Evi-9 编码一种与 BCL-6 相互作用的新型锌指蛋白”Mol.Cel.Biol..（正在出版）。