Post-translational regulation of CD133 by ATase1/ATase2-mediated lysine acetylation.
Post-translational regulation of CD133 by ATase1/ATase2-mediated lysine acetylation.
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DOI：
10.1016/j.jmb.2014.02.012
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发表时间：
2014-05-29
影响因子：
5.6
通讯作者：
Moffat, Jason
中科院分区：
文献类型：
--
作者：
Mak, Anthony B.;Pehar, Mariana;Nixon, Allison M. L.;Williams, Rashida A.;Uetrecht, Andrea C.;Puglielli, Luigi;Moffat, Jason
CD133细胞表面蛋白表达AC133表位，该表位与癌症前体细胞相关，并与传统抗癌治疗的耐药性有关。我们报道了存在乙酰基转移酶的内质网高尔基体中间隔室ATase1和ATase2可以与CD133物理上相互作用，使CD133的三个赖氨酸残基乙酰化，这三个赖氨酸残基预计位于CD133的第一个细胞外环上。这些残基的定点突变模拟了乙酰化的丧失和ATase1/ATase2的下调或抑制，导致CD133蛋白表达几乎完全取消。我们还证明了靶向ATase1/ATase2导致表达CD133的急性淋巴细胞白血病细胞凋亡。综上所述，我们认为预测的胞外残基上的赖氨酸乙酰化在CD133蛋白的表达和向细胞表面的运输中起关键作用，并可以靶向干扰CD133的调节和功能。
The CD133 cell surface protein expresses the AC133 epitope that is associated with cancer progenitor cells and resistance to traditional anticancer therapies. We report that the endoplasmic reticulum Golgi intermediate compartment residing acetyltransferases, ATase1 and ATase2, can physically interact with CD133 to acetylate the protein on three lysine residues predicted to reside on the first extracellular loop of CD133. Site-directed mutagenesis of these residues mimicking a loss of acetylation and downregulation or inhibition of ATase1/ATase2, resulted in near complete abolishment of CD133 protein expression. We also demonstrate that targeting ATase1/ATase2 results in apoptosis of CD133 expressing acute lymphoblastic leukemia cells. Taken together, we suggest that lysine acetylation on predicted extracellular residues plays a key role in expression and trafficking of CD133 protein to the cell surface and can be targeted to disrupt CD133 regulation and function.
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影响因子：
7
作者：
Gisler, Serge M.;Kittanakom, Saranya;Stagljar, Igor
通讯作者：
Stagljar, Igor
DOI：
10.1074/jbc.m111.310136
发表时间：
2012-03-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ding Y;Ko MH;Pehar M;Kotch F;Peters NR;Luo Y;Salamat SM;Puglielli L
通讯作者：
Puglielli L
影响因子：
4
作者：
Jonas, Mary Cabell;Pehar, Mariana;Puglielli, Luigi
通讯作者：
Puglielli, Luigi
影响因子：
4.8
作者：
Mak, Anthony B.;Blakely, Kim M.;Moffat, Jason
通讯作者：
Moffat, Jason
影响因子：
11.2
作者：
Mak, Anthony B.;Nixon, Allison M. L.;Moffat, Jason
通讯作者：
Moffat, Jason