Role of km23-1 in RhoA/actin-based cell migration.
Role of km23-1 in RhoA/actin-based cell migration.
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DOI：
10.1016/j.bbrc.2012.10.047
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发表时间：
2012-11-23
影响因子：
3.1
通讯作者：
Mulder, Kathleen M.
中科院分区：
文献类型：
--
作者：
Jin, Qunyan;Pulipati, Nageswara R.;Zhou, Weidong;Staub, Cory M.;Liotta, Lance A.;Mulder, Kathleen M.
Km23-1最初被鉴定为转化生长因子β受体相互作用蛋白，在转化生长因子β信号转导中发挥重要作用。此外，km23-1实际上是一个古老的NTPase调节蛋白超家族的一部分，在古生菌和细菌中广泛存在。为了进一步阐明km23-1的功能，我们通过串联亲和纯化(TAP)和串联质谱仪(MS)鉴定了km23-1的新的蛋白质相互作用伙伴。在这里，我们展示了km23-1与一类蛋白质的相互作用，这些蛋白质参与了基于肌动蛋白的细胞运动和肌动蛋白细胞骨架的调节。我们进一步表明，km23-1调节了高度组织化的应力纤维网络的形成。更重要的是，我们发现km23-1基因的敲除(KD)降低了Mv1Lu上皮细胞中RhoA的活性。最后，我们的结果首次证明，在伤口愈合试验中，km23-1的缺失抑制了人结肠癌细胞(HCCC)的细胞迁移。总体而言，我们的发现表明km23-1调节RhoA和运动相关的肌动蛋白调节蛋白，表明km23-1可能是抗转移治疗的新靶点。
km23-1 was originally identified as a TGFβ receptor-interacting protein that plays an important role in TGFβ signaling. Moreover, km23-1 is actually part of an ancient superfamily of NTPase-regulatory proteins, widely represented in archaea and bacteria. To further elucidate the function of km23-1, we identified novel protein interacting partners for km23-1 by using tandem affinity purification (TAP) and tandem mass spectrometry (MS). Here we show that km23-1 interacted with a class of proteins involved in actin-based cell motility and modulation of the actin cytoskeleton. We further showed that km23-1 modulates the formation of a highly organized stress fiber network. More significantly, we demonstrated that knockdown (KD) of km23-1 decreased RhoA activation in Mv1Lu epithelial cells. Finally, our results demonstrated for the first time that depletion of km23-1 inhibited cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays. Overall, our findings demonstrate that km23-1 regulates RhoA and motility-associated actin modulating proteins, suggesting that km23-1 may represent a novel target for anti-metastatic therapy.
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影响因子：
11.4
作者：
Miertzschke, Mandy;Koerner, Carolin;Vetter, Ingrid R.;Keilberg, Daniela;Hot, Edina;Leonardy, Simone;Sogaard-Andersen, Lotte;Wittinghofer, Alfred
通讯作者：
Wittinghofer, Alfred
DOI：
10.1083/jcb.200709076
发表时间：
2008-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sakurai-Yageta M;Recchi C;Le Dez G;Sibarita JB;Daviet L;Camonis J;D'Souza-Schorey C;Chavrier P
通讯作者：
Chavrier P
DOI：
10.1186/1478-811x-8-23
发表时间：
2010-09-07
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Parri M;Chiarugi P
通讯作者：
Chiarugi P
影响因子：
3.5
作者：
Jiang, JM;Yu, L;Zhao, SY
通讯作者：
Zhao, SY
影响因子：
4.8
作者：
Jin, Qunyan;Ding, Wei;Mulder, Kathleen M.
通讯作者：
Mulder, Kathleen M.