The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3.
The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3.
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DOI：
10.1186/1476-4598-7-65
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发表时间：
2008-08-07
期刊：
影响因子：
37.3
通讯作者：
Marx SJ
中科院分区：
文献类型：
--
作者：
Agarwal SK;Simonds WF;Marx SJ
在遗传性甲状旁腺功能亢进-颌骨肿瘤综合征、某些甲状旁腺癌和某些家族性甲状旁腺功能亢进的病例中，会发生HRPT2基因的种系和体细胞失活突变。HRPT2编码副纤维蛋白。为了鉴定与副纤维蛋白相互作用的蛋白，我们用酵母双杂交系统筛选了以副纤维蛋白为诱饵的心脏cDNA文库。共分离到14个副纤维蛋白相互作用阳性猎物，分别代表10个独立的肌动蛋白-2基因克隆。副纤维蛋白与肌α-肌动蛋白(Actinin-2和Actinin-3)相互作用，但不与非肌肉α-Actinins(Actinin-1和Actinin-4)相互作用。通过酵母双杂交、GST下拉和免疫共沉淀验证了副纤维蛋白-肌动蛋白的相互作用。酵母双杂交分析表明，副纤维蛋白的N端区域与肌动蛋白相互作用。在肌动蛋白沉积分析中，副纤维蛋白不能将骨骼肌肌动蛋白从肌动蛋白细丝中分离出来，但有趣的是，副纤维蛋白酶也能将肌动蛋白细丝捆绑/交联。在未分化的增殖性成肌细胞(C2C12细胞)中，副纤维蛋白主要分布在细胞核中，而在分化的C2C12肌管中，副纤维蛋白与放线菌素共同定位于胞浆。这些数据支持副纤维蛋白可能通过与肌动蛋白和肌动蛋白的相互作用而在核外发挥作用。这些数据还表明，肌动蛋白(和肌动蛋白)参与隔离细胞质中的副纤维蛋白。
Germline and somatic inactivating mutations in the HRPT2 gene occur in the inherited hyperparathyroidism-jaw tumor syndrome, in some cases of parathyroid cancer and in some cases of familial hyperparathyroidism. HRPT2 encodes parafibromin. To identify parafibromin interacting proteins we used the yeast two-hybrid system for screening a heart cDNA library with parafibromin as the bait. Fourteen parafibromin interaction positive preys representing 10 independent clones encoding actinin-2 were isolated. Parafibromin interacted with muscle alpha-actinins (actinin-2 and actinin-3), but not with non-muscle alpha-actinins (actinin-1 and actinin-4). The parafibromin-actinin interaction was verified by yeast two-hybrid, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid analysis revealed that the N-terminal region of parafibromin interacted with actinins. In actin sedimentation assays parafibromin did not dissociate skeletal muscle actinins from actin filaments, but interestingly, parafibromin could also bundle/cross-link actin filaments. Parafibromin was predominantly nuclear in undifferentiated proliferating myoblasts (C2C12 cells), but in differentiated C2C12 myotubes parafibromin co-localized with actinins in the cytoplasmic compartment. These data support a possible contribution of parafibromin outside the nucleus through its interaction with actinins and actin bundling/cross-linking. These data also suggest that actinins (and actin) participate in sequestering parafibromin in the cytoplasmic compartment.
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DOI：
10.1073/pnas.95.4.1630
发表时间：
1998-02-17
影响因子：
11.1
作者：
Guru, SC;Goldsmith, PK;Chandrasekharappa, SC
通讯作者：
Chandrasekharappa, SC
影响因子：
--
作者：
Otey, CA;Carpen, O
通讯作者：
Carpen, O
影响因子：
3.5
作者：
Mills, MA;Yang, N;North, KN
通讯作者：
North, KN
影响因子：
3.2
作者：
Haven, C. J.;van Puijenbroek, M.;Morreau, H.
通讯作者：
Morreau, H.
影响因子：
3.5
作者：
Hahn, Michael A.;Marsh, Deborah J.
通讯作者：
Marsh, Deborah J.