cDNA cloning and functional analysis of a signal transducer, TRAF5

信号转导器 TRAF5 的 cDNA 克隆和功能分析

• 批准号: 09670341
• 负责人: NAKANO Hiroyasu
• 金额: $ 2.05万
• 依托单位: Juntendo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670341/
• 关键词: TRAF; NF-kappaB; NF-kappaB-inducing kinase; IkappaB kinase; MEKK1; ASK1; knockout mice; CD40; NF-kB; NF-kB-inducing kinase; IkB kinase; MEKKI; ASKI; Lymphotoxin-βレセプター; CD27; CD30; NF-κB.; JNK; ERK

1. We demonstrated that TRAF2 and TRAF5 interact with CD27 and CD3O, and are involved in NF-kappaB activation by these receptors. We also determined the binding domain of CD27 and CD3O for TRAF2 and TRAF5.2. Recently, NF-kappaB kinase (NIK) was identified and has been shown to activate two subunits of the 1kappaB kinase complex, IKKalpha and IKKbeta, both of which directly phosphorylate IkappaBs. We demonstrated that while NIK activates IKKalpha and IKK3b comparably, MEKKI preferentially activates IKKbeta.3. We showed that upon TNF treatment, TRAF2 interacts with apoptosis-regulating kinase 1 (ASK 1) and ASK1 is essential for TRAF2-mediated TNK/SAPK activation.4. To determined the function of TRAF5 in vivo, we generated TRAF5-deficient mice. Despite of no defect of TNF-, CD27-, or CD4O-mediated activation of NF-kappaB or JNK/SAPK in TRAF5-deficient mice, CD4O- and CD27-mediated lymphocyte activation were impaired. These results suggest that a novel function of TRAF5, which is independent on activation of NF-kappaB or JNK/SAPK.

1。我们证明了TRAF2和TRAF5与CD27和CD3O相互作用，并参与了这些受体的NF-kappab激活。我们还确定了TRAF2和TRAF5.2的CD27和CD3O的结合结构域。最近，鉴定了NF-kappab激酶（NIK），并已证明可以激活1Kappab激酶复合物，Ikkalpha和Ikkbeta的两个亚基，这两者都直接磷酸化Ikappab。我们证明，虽然Nik相当激活Ikkalpha和Ikk3b，但Mekki优先激活Ikkbeta.3。我们表明，在TNF处理后，TRAF2与细胞凋亡调节激酶1（ask 1）相互作用，而ASK1对于TRAF2介导的TNK/SAPK激活至关重要。4。为了确定Traf5在体内的功能，我们生成了TRAF5缺陷型小鼠。尽管没有TNF-，CD27-或CD4O介导的NF-kappab或JNK/SAPK在TRAF5缺陷型小鼠中的缺陷，但CD4O和CD27介导的淋巴细胞激活受损。这些结果表明，TRAF5的新功能，它独立于NF-kappab或JNK/SAPK的激活。

项目成果

Nakano, H., M.Shindo, S.Sakon, S.Nishinaka, M.Mihara, H.Yagita, and K.Okumura.: "Differential regulation of IKKalpha and IKKbeta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1." Proc.Natl.Acad.S

Nakano, H.、M.Shindo、S.Sakon、S.Nishinaka、M.Mihara、H.Yagita 和 K.Okumura.：“两种上游激酶（NF-kappaB 诱导激酶和 NF-kappaB 诱导激酶）对 IKKalpha 和 IKKbeta 的差异调节

Nishitoh, H., M.et al.: "ASK1 is essential for JNK/SAPK activation by TRAF2." Molecular Cell. 2. 389-395 (1998)

Nishitoh, H., M.et al.：“ASK1 对于 TRAF2 激活 JNK/SAPK 至关重要。”

Hatakeyama S., M.Kitagawa, K.Nakayama, M.Shirane, M.Matasumoto, K.Hattori, H.Higashi, H.Nakano, K.Okumura, K.Onoe, R.A.Good, and K.-I.Nakayama.Proc.Natl.Acad.Sci.USA: "Ubiquitin-dependent degradation of IkappaB is mediated by a novel ubiquitin ligase SCF^

畠山 S.、M.北川、K.Nakayama、M.Shirane、M.Matasumoto、K.Hattori、H.Higashi、H.Nakano、K.Okumura、K.Onoe、R.A.Good 和 K.-I.Nakayama

Nakano,H.: "Human TNF receptor-associated factor 5 (TRAF5) : cDNA cloning,expression and assignment of TRAF5 gene to chromosome lq32." Genomics. 42. 26-32 (1997)

Nakano,H.：“人 TNF 受体相关因子 5 (TRAF5)：TRAF5 基因的 cDNA 克隆、表达和分配至染色体 lq32。”

Oshima, H., et al.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.10. 517-526 (1998)

Oshima, H. 等人：“通过分子克隆和 mAb 表征鼠 CD70。”