Identification and characterization of a novel folliculin-interacting protein FNIP2
Identification and characterization of a novel folliculin-interacting protein FNIP2
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DOI：
10.1016/j.gene.2008.02.022
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发表时间：
2008-05-31
期刊：
影响因子：
3.5
通讯作者：
Schmidt, Laura S.
中科院分区：
文献类型：
--
作者：
Hasumi, Hisashi;Baba, Masaya;Schmidt, Laura S.
Birt-Hogg-Dube综合征以肾肿瘤风险增加为特征，由编码新型肿瘤抑制蛋白滤泡素（FLCN）的BHD/FLCN基因的种系突变引起，该蛋白与FNIP 1和51-AMP-活化蛋白激酶（AMPK）相互作用。在这里，我们报告了一种新的FNIP 1同源物FNIP 2，也与FLCN和AMPK相互作用的鉴定和表征。C-末端缺失的FLCN突变体，类似于BHD患者中自然发生的种系突变产生的突变体，不能结合FNIP 2。这些数据与我们先前的结果一起表明FNIP 1与FLCN的C-末端结合，表明FLCN肿瘤抑制功能可能通过与FNIP 1和FNIP 2通过其C-末端的相互作用而促进。此外，我们证明，FNIP 1和FNIP 2能够形成同源或异源多聚体，这表明它们可能独立或与FLCN合作发挥作用。FNIP 1和FNIP 2转录本在一些正常组织中的差异表达可能表明这些同源物的组织特异性。有趣的是，FNIP 1和FNIP 2在人肾透明细胞癌（RCC）中相反表达，而在嫌色细胞RCC和嗜酸细胞瘤中协调表达，这表明它们在RCC的不同组织学变体中具有不同的功能。由爱思唯尔公司出版
Birt-Hogg-Dube' syndrome characterized by increased risk for renal neoplasia is caused by germline mutations in the BHD/FLCN gene encoding a novel tumor suppressor protein, folliculin(FLCN), which interacts with FNIP1 and 51-AMP-activated protein kinase(AMPK). Here we report the identification and characterization of a novel FNIP1 homolog FNIP2 that also interacts with FLCN and AMPK. C-terminally-deleted FLCN mutants, similar to those produced by naturally-occurring germline mutations in BHD patients, were unable to bind FNIP2. These data taken together with our previous results that demonstrated FNIP1 binding to the C-terminus of FLCN suggest that FLCN tumor suppressor function may be facilitated by interactions with both FNIP1 and FNIP2 through its C-terminus. Furthermore, we demonstrate that FNIP1 and FNIP2 are able to form homo- or heteromeric multimers suggesting that they may function independently or cooperatively with FLCN. Differential expression of FNIP1 and FNIP2 transcripts in some normal tissues may indicate tissue specificity for these homologs. Interestingly FNIP1 and FNIP2 were oppositely expressed in human clear cell renal cell carcinoma (RCC), and coordinately expressed in chromophobe RCC and oncocytoma, suggesting their differential function in different histologic variants of RCC. Published by Elsevier B.V.