Up-regulation of the Cbl family of ubiquitin ligases is involved in ATRA and bufalin-induced cell adhesion but not cell differentiation
Up-regulation of the Cbl family of ubiquitin ligases is involved in ATRA and bufalin-induced cell adhesion but not cell differentiation
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泛素连接酶 Cbl 家族的上调参与 ATRA 和蟾蜍灵诱导的细胞粘附，但不参与细胞分化
DOI：
10.1016/j.bbrc.2007.12.120
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发表时间：
2008-02-29
影响因子：
3.1
通讯作者：
Hou, Kezou
中科院分区：
文献类型：
--
作者：
Qu, Xiujuan;Liu, Yunpeng;Hou, Kezou
Casitas B 谱系淋巴瘤 (Cbl) 泛素连接酶家族是多功能蛋白，在不同的细胞信号传导通路中发挥重要作用。据报道，在 TPA 诱导的 U937 和 HL-60 细胞分化过程中，c-Cbl 和 Cbl-b mRNA 上调。但泛素连接酶 Cbl 家族的上调机制和作用仍不清楚。在本研究中，我们证明蟾蜍灵增强全反式视黄酸 (ATRA) 诱导的 HL-60 细胞分化，同时上调 Cbl 泛素连接酶家族。 CsA 是一种钙动员抑制剂，可逆转这种上调。 CsA 和 PS-341 预处理不影响 CD11b 的表达，但抑制贴壁细胞的百分比。 Cbl-b 的脂筏定位增强了细胞粘附，而 C 末端缺失部分抑制了这种作用。此外，粘附相关激酶 Pyk2 和 Paxillin 的表达与 Cbl 蛋白的增加同时上调。这些结果表明，c-Cbl和Cbl-b的上调参与了ATRA和蟾蜍灵诱导的HL-60细胞粘附的调节，而不是细胞分化，这可能是由脂筏定位、泛素连接酶活性和Cbl蛋白的C端结构介导的。同时，富含脯氨酸的酪氨酸激酶（Pyk2）和桩蛋白的上调也可能与这种调节有关。 (C) 2007 Elsevier Inc. 保留所有权利。
The Casitas B-lineage Lymphoma (Cbl) family of ubiquitin ligases is multifunctional proteins that play important roles in different cell signaling pathways. It has been reported that c-Cbl and Cbl-b mRNAs are up-regulated during TPA-induced U937 and HL-60 cell differentiation. But the mechanism of the up-regulation and the roles of the Cbl family of ubiquitin ligases still remain unclear. In the present study, we demonstrated that bufalin enhanced all-trans retinoic acid (ATRA) induced differentiation of HL-60 cells, accompanied by up-regulation of the Cbl family of ubiquitin ligases. CsA, an inhibitor of calcium mobilization, reversed this up-regulation. Pretreatment with CsA and PS-341 did not affect the expression of CD11b, but suppressed the percentage of adherent cells. Lipid raft localization of Cbl-b enhanced cell adhesion, while C-terminal deletion partially suppressed the effect. Moreover, the expression of the adhesion-related kinases Pyk2 and Paxillin was up-regulated in parallel with the increase of Cbl proteins. These results suggested that up-regulation of c-Cbl and Cbl-b was involved in the regulation of ATRA and bufalin-induced HL-60 cell adhesion rather than cell differentiation, which might be mediated by lipid raft localization, ubiquitin ligase activity and C-terminal structure of Cbl proteins. Meanwhile, up-regulation of proline-rich tyrosine kinase (Pyk2) and Paxillin might also be implicated in this regulation. (C) 2007 Elsevier Inc. All rights reserved.