Inhibitor of growth 4 induces NFκB/p65 ubiquitin-dependent degradation

被引:49
|
作者
Hou, Y. [1 ]
Zhang, Z. [1 ]
Xu, Q. [1 ]
Wang, H. [2 ]
Xu, Y. [1 ]
Chen, K. [1 ]
机构
[1] Jiangsu Univ, Inst Life Sci, Zhenjiang 2121300, Jiangsu, Peoples R China
[2] Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China
基金
中国国家自然科学基金;
关键词
ING4; NF kappa B/p65; ubiquitination; degradation; NF-KAPPA-B; TUMOR-SUPPRESSOR GENE; CELL-GROWTH; DOWN-REGULATION; ING4; ACTIVATION; APOPTOSIS; PROTEINS; BINDING; LIGASES;
D O I
10.1038/onc.2013.135
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
As a tumor suppressor protein, the inhibitor of growth 4 (ING4) has an important role in many cellular processes including cell cycle progression, proliferation, apoptosis, DNA damage response, tumor angiogenesis and contact inhibition. Here, we report that ING4 functions as an E3 ubiquitin ligase to induce nuclear factor-kappa B (NF kappa B)/p65 degradation. The plant homeodomain finger of ING4 interacted with p65 to undergo robust ubiquitination and degradation. ING4 bound to p65 and delivered the Lys-48-linked polyubiquitin to Lys-62 residue of p65, leading to ubiquitination of p65 and degradation. Lys-62 residue of p65 was required for ING4-mediated ubiquitination of p65 and degradation. Further analysis shows that C239 of ING4 was critical for ING4-induced p65 degradation. These findings demonstrate that ING4 acts as an E3 ubiquitin ligase to induce ubiquitination of p65 and degradation, which is critical to terminate NFkB activation.
引用
收藏
页码:1997 / 2003
页数:7
相关论文
共 50 条
  • [21] Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-B p65 signaling
    Cheng, Qiong
    Du, Juan
    Xie, Lin
    Liu, Xiao
    Li, Zheng
    Zuo, Fuguo
    Wu, Jinfeng
    Xu, Jinhua
    ONCOLOGY REPORTS, 2018, 40 (01) : 369 - 376
  • [22] Degradation of antizyme inhibitor, an ornithine decarboxylase homologous protein, is ubiquitin-dependent and is inhibited by antizyme
    Bercovich, Z
    Kahana, C
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (52) : 54097 - 54102
  • [23] INVITRO DEGRADATION OF P450IIE1 BY UBIQUITIN-DEPENDENT PROTEOLYSIS
    KOOP, DR
    TIERNEY, DJ
    HAAS, AL
    FASEB JOURNAL, 1991, 5 (06): : A1514 - A1514
  • [24] Ubiquitin-dependent and -independent proteasomal degradation of hepatitis B virus X protein
    Kim, Jung-Hwan
    Sohn, Sook-Young
    Yen, T. S. Benedict
    Ahn, Byung-Yoon
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 366 (04) : 1036 - 1042
  • [25] Ubiquitin-dependent degradation of cyclin B is accelerated during an endomitotic cell cycle
    Zhang, Y
    Wang, Z
    Pagano, M
    Ravid, K
    FASEB JOURNAL, 1997, 11 (09): : A1217 - A1217
  • [26] Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis
    Zhou, Haoxiong
    Wan, Sizhe
    Luo, Yujun
    Liu, Huiling
    Jiang, Jie
    Guo, Yunwei
    Xiao, Jia
    Wu, Bin
    GASTROENTEROLOGY REPORT, 2023, 11
  • [27] DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation
    Haoran Cui
    Qin Wang
    Zhenchuan Lei
    Maoxiao Feng
    Zhongxi Zhao
    Yunshan Wang
    Guangwei Wei
    Journal of Experimental & Clinical Cancer Research, 38
  • [28] Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1
    Hattori, Takayuki
    Isobe, Tomoyasu
    Abe, Kenji
    Kikuchi, Hirotoshi
    Kitagawa, Kyoko
    Oda, Toshiaki
    Uchida, Chiharu
    Kitagawa, Masatoshi
    CANCER RESEARCH, 2007, 67 (22) : 10789 - 10795
  • [29] Activating transcription factor 4 regulates RET autophosphorylation and ubiquitin-dependent degradation
    Bagheri-Yarmand, Rozita
    Cote, Gilbert J.
    Gagel, Robert F.
    CANCER RESEARCH, 2014, 74 (19)
  • [30] DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation
    Cui, Haoran
    Wang, Qin
    Lei, Zhenchuan
    Feng, Maoxiao
    Zhao, Zhongxi
    Wang, Yunshan
    Wei, Guangwei
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2019, 38 (01)