HM1.24/BST-2 is constitutively poly-ubiquitinated at the N-terminal amino acid in the cytoplasmic domain
HM1.24/BST-2 is constitutively poly-ubiquitinated at the N-terminal amino acid in the cytoplasmic domain
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HM1.24/BST-2 在胞质结构域的 N 末端氨基酸处被组成型多泛素化
DOI：
10.1016/j.bbrep.2020.100784
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发表时间：
2020
影响因子：
2.7
通讯作者：
Tanaka Yoshitaka
中科院分区：
文献类型：
--
作者：
Fujimoto Keiko;Nakashima Sanae;Uchida Shotaro;Amen Riham N.S.;Ishii Yuji;Hirota Yuko;Tanaka Yoshitaka
HM1.24(也称为BST-2、CD317和Tetherin)是一种II型单程跨膜糖蛋白，它利用N端的跨膜螺旋穿过膜，并通过C端的糖基磷脂酰肌醇(GPI)锚定在膜脂筏中。HM1.24在多种细胞功能中发挥作用，包括细胞信号、免疫调节和恶性肿瘤。此外，它还作为干扰素诱导的细胞抗病毒限制因子，抑制不同包膜病毒的复制和释放，并被HIV-1辅助蛋白VPU所抵消。VPU诱导HM1.24胞浆区域的下调和泛素结合。然而，关于HM1.24泛素化位点(S)的证据仍然存在争议。我们证明了HM1.24在N-末端胞浆区域是结构性的多泛素化的，并且所有潜在的泛素化位点的突变，包括HM1.24胞浆区域的丝氨酸、苏氨酸、半胱氨酸和赖氨酸，并不影响HM1.24的泛素化。我们进一步证明，虽然GPI锚点对于HM1.24的抗病毒活性和捕获病毒粒子是必要的和充分的，但GPI的缺失突变体并不影响HM1.24的泛素化。这些结果表明，HM1.24的脂筏定位不是泛素化的先决条件。总之，我们的发现证明HM1.24的泛素化发生在细胞质区域的N-末端氨基酸上，并表明HM1.24的构成泛素化机制可能不同于VPU诱导的泛素化机制。
HM1.24 (also known as BST-2, CD317, and Tetherin) is a type II single-pass transmembrane glycoprotein, which traverses membranes using an N-terminal transmembrane helix and is anchored in membrane lipid rafts via a C-terminal glycosylphosphatidylinositol (GPI). HM1.24 plays a role in diverse cellular functions, including cell signaling, immune modulation, and malignancy. In addition, it also functions as an interferon-induced cellular antiviral restriction factor that inhibits the replication and release of diverse enveloped viruses, and which is counteracted by Vpu, an HIV-1 accessory protein. Vpu induces down-regulation and ubiquitin conjugation to the cytoplasmic domain of HM1.24. However, evidence for ubiquitination site(s) of HM1.24 remains controversial. We demonstrated that HM1.24 is constitutively poly-ubiquitinated at the N-terminal cytoplasmic domain, and that the mutation of all potential ubiquitination sites, including serine, threonine, cysteine, and lysine in the cytoplasmic domain of HM1.24, does not affect the ubiquitination of HM1.24. We further demonstrated that although a GPI anchor is necessary and sufficient for HM1.24 antiviral activities and virion-trapping, the deleted mutant of GPI does not influence the ubiquitination of HM1.24. These results suggest that the lipid raft localization of HM1.24 is not a prerequisite for the ubiquitination. Collectively, our findings demonstrate that the ubiquitination of HM1.24 occurs at the N-terminal amino acid in the cytoplasmic domain and indicate that the constitutive ubiquitination machinery of HM1.24 may differ from the Vpu-induced machinery.
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影响因子：
30.3
作者：
Hinz A;Miguet N;Natrajan G;Usami Y;Yamanaka H;Renesto P;Hartlieb B;McCarthy AA;Simorre JP;Göttlinger H;Weissenhorn W
通讯作者：
Weissenhorn W
抗原依赖性内化与人源化抗 HM1 从血浆中的快速消除有关。
DOI：
--
发表时间：
2010
期刊：
Drug Metab. Dispos.
影响因子：
--
作者：
Amano J.;Masuyama N.;Hirota Y.;Tanaka Y.;Igawa Y.;Shiokawa R.;Okutani T.;Miyayama T.;Nanami M.;and Ishigai M.
通讯作者：
and Ishigai M.
影响因子：
11.2
作者：
Jennifer Walter-Yohrling;Xiaohong Cao;Michele Callahan;W. Weber;S. Morgenbesser;S. Madden;Clarence J. Wang;B. Teicher
通讯作者：
Jennifer Walter-Yohrling;Xiaohong Cao;Michele Callahan;W. Weber;S. Morgenbesser;S. Madden;Clarence J. Wang;B. Teicher
影响因子：
20.3
作者：
Tetsuya Goto;Stephen J. Kennel;Masahiro Abe;Makoto Takishita;Masaaki Kosaka;Alan Solomon;Shiro Saito-S
通讯作者：
Tetsuya Goto;Stephen J. Kennel;Masahiro Abe;Makoto Takishita;Masaaki Kosaka;Alan Solomon;Shiro Saito-S
影响因子：
7.5
作者：
Piper, Robert C.;Luzio, J. Paul
通讯作者：
Luzio, J. Paul