更新于：2024-11-01

ubiquitin x TOB2

更新于：2024-11-01

基本信息

关联

项与 ubiquitin x TOB2 相关的药物

S115

靶点

TOB2 x ubiquitin

作用机制

TOB2 agonists [+2]

在研机构

上海交通大学

原研机构

上海交通大学

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ubiquitin x TOB2 相关的临床结果

登录后查看更多信息

100 项与 ubiquitin x TOB2 相关的转化医学

登录后查看更多信息

0 项与 ubiquitin x TOB2 相关的专利（医药）

登录后查看更多信息

项与 ubiquitin x TOB2 相关的文献（医药）

2014-10-01·Acta Pharmacologica Sinica1区 · 医学

Characterization of the anticancer effects of S115, a novel heteroaromatic thiosemicarbazone compound, in vitro and in vivo

1区 · 医学

Article

作者: Cai, Li ; Xiong, Wei-xia ; Liu, Ying ; Yin, Ming ; Liu, Quan-hai ; Liu, Min-yu ; Yao, Yu-long ; Dong, Yu-qiong ; Xiao, Lin

AIMTo investigate the anticancer effects of S115, a novel heteroaromatic thiosemicarbazone compound in vitro and in vivo.METHODSThe anti-proliferative action of S115 was analyzed in 12 human and mouse cancer cell lines using MTT assay. Autograft and xenograft cancer models were made by subcutaneous inoculation of cancer cells into mice or nude mice. The mice were orally treated with S115 (2, 8, 32 mg·kg(-1)·d(-1)) for 7 d, and the tumor size was measured every 3 d. Cell apoptosis and cell cycle distribution were examined using flow cytometry, gene expression profile analyses, Western blots and RT-PCR.RESULTSThe IC50 values of S115 against 12 human and mouse cancer cell lines ranged from 0.3 to 6.6 μmol/L. The tumor growth inhibition rate caused by oral administration of S115 (32 mg·kg(-1)·d(-1)) were 89.7%, 81.7%, 78.4% and 77.8%, respectively, in mouse model of B16 melanoma, mouse model of Colon26 colon cancer, nude mouse model of A549 lung cancer and nude mouse model of SK-OV-3 ovarian cancer. Furthermore, oral administration of S115 (7.5 mg·kg(-1)·d(-1)) synergistically enhanced the anticancer effects of cyclophosphamide, cisplatin, or 5-fluorouracil in mouse model of S180 sarcoma. Treatment of A549 human lung cancer cells with S115 (1.5 μmol/L) induced G0/G1 cell cycle arrest, and increased apoptosis. Furthermore, S115 downregulated the level of ubiquitin, and upregulated the level of Tob2 in A549 cells.CONCLUSIONS115 exerts anticancer effects against a variety of cancer cells in vitro and in grafted cancer models by inducing apoptosis, downregulating ubiquitin and upregulating Tob2.

2014-01-01·Molecular & Cellular Proteomics1区 · 生物学

Peptide Level Immunoaffinity Enrichment Enhances Ubiquitination Site Identification on Individual Proteins

1区 · 生物学

Article

作者: Jennie R. Lill ; Veronica G. Anania ; Victoria C. Pham ; Donald S. Kirkpatrick ; XiaoDong Huang ; Alexandre Masselot

Ubiquitination is a process that involves the covalent attachment of the 76-residue ubiquitin protein through its C-terminal di-glycine (GG) to lysine (K) residues on substrate proteins. This post-translational modification elicits a wide range of functional consequences including targeting proteins for proteasomal degradation, altering subcellular trafficking events, and facilitating protein-protein interactions. A number of methods exist for identifying the sites of ubiquitination on proteins of interest, including site-directed mutagenesis and affinity-purification mass spectrometry (AP-MS). Recent publications have also highlighted the use of peptide-level immunoaffinity enrichment of K-GG modified peptides from whole cell lysates for global characterization of ubiquitination sites. Here we investigated the utility of this technique for focused mapping of ubiquitination sites on individual proteins. For a series of membrane-associated and cytoplasmic substrates including erbB-2 (HER2), Dishevelled-2 (DVL2), and T cell receptor α (TCRα), we observed that K-GG peptide immunoaffinity enrichment consistently yielded additional ubiquitination sites beyond those identified in protein level AP-MS experiments. To assess this quantitatively, SILAC-labeled lysates were prepared and used to compare the abundances of individual K-GG peptides from samples prepared in parallel. Consistently, K-GG peptide immunoaffinity enrichment yielded greater than fourfold higher levels of modified peptides than AP-MS approaches. Using this approach, we went on to characterize inducible ubiquitination on multiple members of the T-cell receptor complex that are functionally affected by endoplasmic reticulum (ER) stress. Together, these data demonstrate the utility of immunoaffinity peptide enrichment for single protein ubiquitination site analysis and provide insights into the ubiquitination of HER2, DVL2, and proteins in the T-cell receptor complex.

2002-07-01·European Journal of Biochemistry

Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin‐proteasome system

Article

作者: Hitoshi Sasajima ; Hideyoshi Yokosawa ; Koji Nakagawa

BTG/Tob family proteins, which are characterized by similarities in their N‐terminal BTG/Tob homology domains, control cell growth negatively. Among the BTG/Tob family members, BTG2/TIS21/PC3 proteins have been reported to have short lives and to be degraded by the proteasome. However, the mechanisms regulating the stabilities of other BTG/Tob family proteins have not yet been clarified. Here, we report that BTG1, Tob, and Tob2 proteins, as well as BTG2 protein, are degraded by the ubiquitin–proteasome system; the degradation of Tob protein in HeLa cells and the degradation of BTG1, BTG2, Tob and Tob2 proteins transiently expressed in HEK293 cells were inhibited by treatments with proteasome‐specific inhibitors. Co‐expression of BTG1, BTG2, Tob, or Tob2 protein with ubiquitin in HEK293 cells revealed specific multiubiquitination of each of the four proteins. Although the full‐length and N‐terminal truncated forms of BTG1, BTG2, Tob, and Tob2 proteins were unstable, the respective C‐terminal truncated forms were found to be almost stable, suggesting that the C‐terminal regions control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins. In addition, it was found that the respective C‐terminal regions confer instability on green fluorescent protein, a normally stable protein. Thus, it can be concluded that the C‐terminal regions are necessary and sufficient to control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins.