LASS5 Interacts with SDHB and Synergistically Represses p53 and p21 Activity.
LASS5 Interacts with SDHB and Synergistically Represses p53 and p21 Activity.
复制标题
LASS5 与 SDHB 相互作用并协同抑制 p53 和 p21 活性
DOI：
10.2174/1566524016666160607090012
复制
发表时间：
2016
影响因子：
2.5
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Jiang Z;Li F;Wan Y;Han Z;Yuan W;Cao L;Deng Y;Peng X;Chen F;Fan X;Liu X;Dai G;Wang Y;Zeng Q;Shi Y;Zhou Z;Chen Y;Xu W;Luo S;Chen S;Ye X;Mo X;Wu X;Li Y
Longevity Assurance 5（LASS 5）是LASS/神经酰胺合成酶家族的成员，合成C16-神经酰胺，与肿瘤生物学有关。然而，其确切作用尚不清楚。使用人cDNA文库进行酵母双杂交筛选以鉴定潜在的LASS 5相互作用伴侣。一个鉴定的克隆编码琥珀酸脱氢酶亚基B（SDHB）。哺乳动物双杂交实验表明LASS 5与SDHB相互作用，GST pull-down和免疫共沉淀实验也证实了这一结果。SDHB的C-末端片段是相互作用所必需的。LASS 5和SDHB在COS-7细胞中共定位。LASS 5和SDHB在神经胶质瘤组织中表达上调。转染试验表明，LASS 5或SDHB表达抑制p53或p21报告活性，分别。同时LASS 5和SDHB表达导致p53和p21报告活性的更强抑制，表明LASS 5和SDHB相互作用可能协同影响p53和p21的转录调控。我们的数据为LASS 5和SDHB在肿瘤生物学中的潜在作用提供了新的分子见解。
Longevity Assurance 5 (LASS5), a member of the LASS/Ceramide Synthases family, synthesizes C16-ceramide and is implicated in tumor biology. However, its precise role is not yet well understood. A yeast two-hybrid screen was performed using a human cDNA library to identify potential LASS5- interaction partners. One identified clone encodes succinate dehydrogenase subunit B (SDHB). Mammalian two-hybrid assays showed that LASS5 interacts with SDHB, and the result was also confirmed by GST pull-down and coimmunoprecipitation assays. The C-terminal fragment of SDHB was required for the interaction. LASS5 and SDHB were co-localized in COS-7 cells. LASS5 and SDHB expressions were found to be up-regulated in neuroglioma tissue. Transfection assays showed that LASS5 or SDHB expression repressed p53 or p21 reporter activity, respectively. Simultaneous LASS5 and SDHB expression resulted in stronger repression of p53 and p21 reporter activity, suggesting that LASS5 and SDHB interaction may synergistically affect transcriptional regulation of p53 and p21. Our data provide new molecular insights into potential roles of LASS5 and SDHB in tumor biology.