CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-κB
CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-κB
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DOI：
10.1074/jbc.c000726200
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发表时间：
2000-12-29
影响因子：
4.8
通讯作者：
Alnemri, ES
中科院分区：
文献类型：
--
作者：
Bertin, J;Guo, Y;Alnemri, ES
BCL 10/CLAP是细胞凋亡和NF-κ B信号通路的激活剂，并与粘膜相关淋巴组织的B细胞淋巴瘤有关。尽管BCL 10在细胞凋亡中的作用仍有待确定，但它可能通过IKK复合物激活NF-κ B以响应上游刺激。BCL 10的N端半胱天冬酶募集结构域（CARD）被认为是一个激活结构域，介导与上游含有CARD的NF-κ B激活剂的血友病相互作用。为了鉴定BCL 10的上游信号传导伙伴，我们进行了哺乳动物双杂交分析，并鉴定了BCL 10作为一种新的含CARD的蛋白，其选择性地与BCL 10的CARD激活结构域相互作用。当在细胞中表达时，BCL 10结合并激活NF-κ B。此外，发现内源性BCL 10与BCL 10相关，表明两种蛋白质在细胞内形成预先存在的信号传导复合物。C2 H4也自缔合，并含有广泛的卷曲螺旋基序，可以作为寡聚化结构域。我们在这里提出，BCL 10和NF-κ B信号的上游激活剂。
BCL10/CLAP is an activator of apoptosis and NF-kappaB signaling pathways and has been implicated in B cell lymphomas of mucosa-associated lymphoid tissue. Although its role in apoptosis remains to be determined, BCL10 likely activates NF-kappaB through the IKK complex in response to upstream stimuli. The N-terminal caspase recruitment domain (CARD) of BCL10 has been proposed to function as an activation domain that mediates hemophilic interactions with an upstream CARD-containing NF-kappaB activator. To identify upstream signaling partners of BCL10, we performed a mammalian two-hybrid analysis and identified CARDS as a novel CARD-containing protein that interacts selectively with the CARD activation domain of BCL10. When expressed in cells, CARDS binds to BCL10 and activates NF-kappaB. Furthermore, endogenous CARDS is found associated with BCL10 suggesting that both proteins form a pre-existing signaling complex within cells. CARDS also self-associates and contains extensive coiled-coil motifs that may function as oligomerization domains. We propose here that CARDS is an upstream activator of BCL10 and NF-kappaB signaling.