The SARAH Domain of RASSF1A and Its Tumor Suppressor Function.
The SARAH Domain of RASSF1A and Its Tumor Suppressor Function.
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RASSF1A的Sarah域及其肿瘤抑制功能。
DOI：
10.1155/2012/196715
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Dammann RH
中科院分区：
文献类型：
--
作者：
Dittfeld C;Richter AM;Steinmann K;Klagge-Ulonska A;Dammann RH
Ras关联结构域家族1A （RASSF1A）肿瘤抑制子编码一个Sav-RASSF-Hpo结构域（SARAH），这是一个以hWW45 （dSAV）和MST1/2 （dHpo）为特征的相互作用结构域。在我们的研究中，RASSF1A和RASSF1C与MST1和MST2之间的相互作用被证实，并且表明这种相互作用依赖于SARAH结构域。SARAH结构域缺失的RASSF1A具有与全长RASSF1A相似的生长抑制作用，并显著抑制肺癌细胞系A549的锚定独立生长。在表达SARAH缺失形式RASSF1A的癌细胞中，与全长RASSF1A相比，有丝分裂率降低（P = 0.001），中期异常（P < 0.001），凋亡率显著增加（P = 0.006）。尽管与微管的关联及其稳定性不受影响，但RASSF1A的SARAH结构域的缺失改变了有丝分裂纺锤体的形成。综上所述，我们的研究结果表明SARAH结构域在调控RASSF1A的功能中起着重要作用。
The Ras association domain family 1A (RASSF1A) tumor suppressor encodes a Sav-RASSF-Hpo domain (SARAH), which is an interaction domain characterized by hWW45 (dSAV) and MST1/2 (dHpo). In our study, the interaction between RASSF1A and RASSF1C with MST1 and MST2 was demonstrated and it was shown that this interaction depends on the SARAH domain. SARAH domain-deleted RASSF1A had a similar growth-reducing effect as full-length RASSF1A and inhibited anchorage independent growth of the lung cancer cell lines A549 significantly. In cancer cells expressing the SARAH deleted form of RASSF1A, reduced mitotic rates (P = 0.001) with abnormal metaphases (P < 0.001) were observed and a significantly increased rate of apoptosis was found (P = 0.006) compared to full-length RASSF1A. Although the association with microtubules and their stabilization was unaffected, mitotic spindle formation was altered by deletion of the SARAH domain of RASSF1A. In summary, our results suggest that the SARAH domain plays an important role in regulating the function of RASSF1A.