Ubiquitin ligases

Definition

Ubiquitin ligases are enzymes involved in the ligation step of ubiquitylation. Ubiquitin ligases bind the substrate protein and catalyse the transfer of ubiquitin from the cysteine of ubiquitin-conjugating enzymes to a lysine residue on the substrate protein.

Latest Research and Reviews

  • Research | | open

    Ubiquitin ligases play critical roles in neuronal connectivity in the brain. Here, Valnegri and colleagues show that ubiquitin ligase RNF8 and ubiquitin-conjugating enzyme UBC13 regulate synapse number in cerebellar granule neurons and rodent cerebellar learning.

    • Pamela Valnegri
    • , Ju Huang
    • , Tomoko Yamada
    • , Yue Yang
    • , Luis A. Mejia
    • , Ha Y. Cho
    • , Anna Oldenborg
    •  & Azad Bonni
  • Research |

    Mutations in SPOP, the gene encoding a component of the E3 ubiquitin ligase complex, impair ubiquitination-dependent degradation of BRD2, BRD3 and BRD4 proteins and result in activation of ATK–mTORC1 signaling and resistance to BET inhibitors. Pharmacological blockade of AKT represents a viable strategy to restore the sensitivity of SPOP-mutant prostate tumors to BET inhibitors. These results, together with findings by Dai et al. and Janouskova et al., uncover a new nongenetic mechanism of resistance to BET inhibition involving cancer-type-specific mutations in SPOP, and support the evaluation of SPOP mutation status to inform the administration of BET inhibitors in the clinic.

    • Pingzhao Zhang
    • , Dejie Wang
    • , Yu Zhao
    • , Shancheng Ren
    • , Kun Gao
    • , Zhenqing Ye
    • , Shangqian Wang
    • , Chun-Wu Pan
    • , Yasheng Zhu
    • , Yuqian Yan
    • , Yinhui Yang
    • , Di Wu
    • , Yundong He
    • , Jun Zhang
    • , Daru Lu
    • , Xiuping Liu
    • , Long Yu
    • , Shimin Zhao
    • , Yao Li
    • , Dong Lin
    • , Yuzhuo Wang
    • , Liguo Wang
    • , Yu Chen
    • , Yinghao Sun
    • , Chenji Wang
    •  & Haojie Huang
    Nature Medicine 23, 1055–1062
  • Research |

    Recurrent mutations in SPOP-encoding a Cullin 3-based E3 ubiquitin ligase- in prostate cancer disrupt the recognition and degradation of ubiquitination substrates, including BET proteins. Consequently, stability of BET proteins is enhanced and this increases the resistance to BET inhibitors in SPOP-mutant prostate tumors. These results, together with those in Janouskova et al. and Zhang et al., uncover a novel non genetic mechanism of resistance to BET inhibition involving cancer type-specific mutations in SPOP, and support the evaluation of SPOP mutations to inform the administration of BET inhibitors in the clinic.

    • Xiangpeng Dai
    • , Wenjian Gan
    • , Xiaoning Li
    • , Shangqian Wang
    • , Wei Zhang
    • , Ling Huang
    • , Shengwu Liu
    • , Qing Zhong
    • , Jianping Guo
    • , Jinfang Zhang
    • , Ting Chen
    • , Kouhei Shimizu
    • , Francisco Beca
    • , Mirjam Blattner
    • , Divya Vasudevan
    • , Dennis L Buckley
    • , Jun Qi
    • , Lorenz Buser
    • , Pengda Liu
    • , Hiroyuki Inuzuka
    • , Andrew H Beck
    • , Liewei Wang
    • , Peter J Wild
    • , Levi A Garraway
    • , Mark A Rubin
    • , Christopher E Barbieri
    • , Kwok-Kin Wong
    • , Senthil K Muthuswamy
    • , Jiaoti Huang
    • , Yu Chen
    • , James E Bradner
    •  & Wenyi Wei
    Nature Medicine 23, 1063–1071
  • Research | | open

    Protein stability modulation by E3 ubiquitin ligases is an important layer of functional regulation, but screening for E3 ligase-substrate interactions is time-consuming and costly. Here, the authors take an in silico naïve Bayesian classifier approach to integrate multiple lines of evidence for E3-substrate prediction, enabling prediction of the proteome-wide human E3 ligase interaction network.

    • Yang Li
    • , Ping Xie
    • , Liang Lu
    • , Jian Wang
    • , Lihong Diao
    • , Zhongyang Liu
    • , Feifei Guo
    • , Yangzhige He
    • , Yuan Liu
    • , Qin Huang
    • , Han Liang
    • , Dong Li
    •  & Fuchu He

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