FBXO25, an F-box protein homologue of atrogin-1, is not induced in atrophying muscle
FBXO25, an F-box protein homologue of atrogin-1, is not induced in atrophying muscle
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DOI：
10.1016/j.bbagen.2006.03.020
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发表时间：
2006-06-01
影响因子：
3
通讯作者：
Gomes, Marcelo D.
中科院分区：
文献类型：
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作者：
Maragno, Ana Leticia G. C.;Baqui, Munira M. A.;Gomes, Marcelo D.
Atrogin-1/TN 4AFbx/FBXO 32是一种肌肉特异性泛素连接酶（0），在萎缩的肌肉中显著增加。在这里，我们研究了atrogin-1和FBXO 25之间的功能关系，FBXO 25具有65%的氨基酸同一性。使用RT-PCR，我们证明了FBXO 25在脑，肾和肠中高度表达，而atrogin-1的表达主要限于横纹肌。FBXO 25在这里被证明含有一个功能性的F盒结构域，该结构域与Skp 1结合，从而与SCF型E3的主要成分Roc 1和Cull结合。此外，含有FBXO 25的生产性SCF复合物显示出泛素连接酶活性。我们研究了atroginI和FBX 025在禁食和地塞米松治疗的小鼠以及链脲佐菌素诱导的糖尿病大鼠中的差异表达。虽然atrogin-1在所有三种模型中在肌肉中被强烈诱导，但在FBX 025的表达中没有观察到变化。因此，在这里，我们已经表明，FBX 025是一种新的F盒蛋白类似于atrogin-1，这是不参与肌肉萎缩。进一步的功能研究应该阐明FBX 025在泛素-蛋白酶体途径中的确切作用。(c)2006 Elsevier B. V.保留所有权利。
Atrogin-1/TN4AFbx/FBXO32 is a muscle-specific ubiquitin-ligase (0) that is dramatically increased in atrophying muscle. Here, we have investigated the functional relationship between atrogin-1 and FBXO25 which shares 65% amino acid identity. Using a RT-PCR, we demonstrated that FBXO25 is highly expressed in brain, kidney, and intestine, whereas atrogin-1 expression is largely restricted to striate muscle. FBXO25 was shown here to contain a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cull, the major components of SCF-type E3s. In addition, the productive SCF complex containing FBXO25 showed ubiquitin ligase activity. We investigated the differential expression of atroginI and FBX025 in fasted and dexamethasone-treated mice and also in rats with streptozotocin-induced diabetes. Although the atrogin-1 was strongly induced in muscle in all three models, no changes were observed in the expression of FBX025. Therefore, here we have shown that FBX025 is a novel F-box protein analogous to atrogin-1, which is not involved in muscle atrophy. Further functional studies should elucidate the exact role of FBX025 in the ubiquitin-proteasome pathway. (c) 2006 Elsevier B.V. All rights reserved.