An HECT domain ubiquitin ligase CgWWP1 regulates granulocytes proliferation in oyster Crassostrea gigas

2021 ◽  
Vol 123 ◽  
pp. 104148
Author(s):  
Ying Song ◽  
Xiaorui Song ◽  
Dan Zhang ◽  
Ying Yang ◽  
Lingling Wang ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Crassostrea Gigas ◽  
Hect Domain

scholarly journals The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein

2008 ◽  
Vol 10 (6) ◽  
pp. 643-653 ◽  
Author(s):  
Xudong Zhao ◽  
Julian Ik-Tsen Heng ◽  
Daniele Guardavaccaro ◽  
Richeng Jiang ◽  
Michele Pagano ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Neural Differentiation ◽  
Hect Domain ◽  
Differentiation And Proliferation

scholarly journals Degradation of Tyrosine Phosphatase PTPN3 (PTPH1) by Association with Oncogenic HumanPapillomavirus E6 Proteins

2006 ◽  
Vol 81 (5) ◽  
pp. 2231-2239 ◽  
Author(s):  
Ming Jing ◽  
Joanna Bohl ◽  
Nicole Brimer ◽  
Michael Kinter ◽  
Scott B. Vande Pol
Keyword(s):  
Growth Factor ◽  
Ubiquitin Ligase ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Pdz Domain ◽  
Hect Domain ◽  
Hpv E6 ◽  
Colon Cancers ◽  
Tumor Viruses

ABSTRACT Oncoproteins from DNA tumor viruses associate with critical cellular proteins to regulate cell proliferation, survival, and differentiation.Human papillomavirus (HPV) E6 oncoproteins have been previously shown to associate with a cellular HECT domain ubiquitin ligase termed E6AP (UBE3A). Here we show that the E6-E6AP complex associates with and targets the degradation of the protein tyrosine phosphatase PTPN3 (PTPH1) in vitro and in living cells. PTPN3 is a membrane-associated tyrosine phosphatase with FERM, PDZ, and PTP domains previously implicated in regulating tyrosine phosphorylation of growth factor receptors and p97 VCP (valosin-containing protein, termed Cdc48 in Saccharomyces cerevisiae) and is mutated in a subset of colon cancers. Degradation of PTPN3 by E6 requires E6AP, the proteasome, and an interaction between the carboxy terminus of E6 and the PDZ domain of PTPN3. In transduced keratinocytes, E6 confers reduced growth factor requirements, a function that requires the PDZ ligand of E6 and that can in part be replicated by inhibiting the expression of PTPN3. This report demonstrates the potential of E6 to regulate phosphotyrosine metabolism through the targeted degradation of a tyrosine phosphatase.

scholarly journals Selective compounds enhance osteoblastic activity by targeting HECT domain of ubiquitin ligase Smurf1

Oncotarget ◽  
2016 ◽  
Vol 8 (31) ◽  
pp. 50521-50533 ◽  
Author(s):  
Yuan Zhang ◽  
Cheng Wang ◽  
Yu Cao ◽  
Yongqing Gu ◽  
Lingqiang Zhang
Keyword(s):  
Ubiquitin Ligase ◽  
Hect Domain ◽  
Osteoblastic Activity

scholarly journals WW domain–mediated regulation and activation of E3 ubiquitin ligase Suppressor of Deltex

2018 ◽  
Vol 293 (43) ◽  
pp. 16697-16708 ◽  
Author(s):  
Weiyi Yao ◽  
Zelin Shan ◽  
Aihong Gu ◽  
Minjie Fu ◽  
Zhifeng Shi ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Cell Cycle Progression ◽  
Regulatory Mechanism ◽  
Cycle Progression ◽  
Hect Domain ◽  
Ww Domain ◽  
Ww Domains ◽  
E3 Ligases ◽  
Regulation Of Cell Cycle ◽  
Py Motif

The Nedd4 family E3 ligases Itch and WWP1/2 play crucial roles in the regulation of cell cycle progression and apoptosis and are closely correlated with cancer development and metastasis. It has been recently shown that the ligase activities of Itch and WWP1/2 are tightly regulated, with the HECT domain sequestered intramolecularly by a linker region connecting WW2 and WW3. Here, we show that a similar autoinhibitory mechanism is utilized by the Drosophila ortholog of Itch and WWP1/2, Suppressor of Deltex (Su(dx)). We show that Su(dx) adopts an inactive steady state with the WW domain region interacting with the HECT domain. We demonstrate that both the linker and preceding WW2 are required for the efficient binding and regulation of Su(dx) HECT. Recruiting the multiple-PY motif–containing adaptor dNdfip via WW domains relieves the inhibitory state of Su(dx) and leads to substrate (e.g. Notch) ubiquitination. Our study demonstrates an evolutionarily conservative mechanism governing the regulation and activation of some Nedd4 family E3 ligases. Our results also suggest a dual regulatory mechanism for specific Notch down-regulation via dNdfip–Su(dx)–mediated Notch ubiquitination.

scholarly journals Direct Binding to Rsp5p Regulates Ubiquitination-independent Vacuolar Transport of Sna3p

2007 ◽  
Vol 18 (5) ◽  
pp. 1781-1789 ◽  
Author(s):  
Hadiya Watson ◽  
Juan S. Bonifacino
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ubiquitin Ligase ◽  
Adaptor Protein ◽  
Direct Interaction ◽  
Integral Membrane Proteins ◽  
Multivesicular Bodies ◽  
Hect Domain ◽  
Ww Domains ◽  
Cytosolic Domains ◽  
Direct Binding

The sorting of integral membrane proteins such as carboxypeptidase S (Cps1p) into the luminal vesicles of multivesicular bodies (MVBs) in Saccharomyces cerevisiae requires ubiquitination of their cytosolic domains by the ubiquitin ligases Rsp5p and/or Tul1p. An exception is Sna3p, which does not require ubiquitination for entry into MVBs. The mechanism underlying this ubiquitination-independent MVB sorting pathway has not yet been characterized. Here, we show that Sna3p sorting into the MVB pathway depends on a direct interaction between a PPAY motif within its C-terminal cytosolic tail and the WW domains of Rsp5p. Disruption of this interaction inhibits vacuolar targeting of Sna3p and causes its accumulation in a compartment that overlaps only partially with MVBs. Surprisingly, Sna3p does require a functional ubiquitin-ligase HECT domain within Rsp5p; however, the dependence of Sna3p on HECT domain activity is distinct from that of Cps1p. Last, we show that Sna3p requires neither Tul1p nor the transmembrane adaptor protein Bsd2p for its MVB sorting. Our data demonstrate that Sna3p follows a novel ubiquitination-independent, but Rsp5p-mediated, sorting pathway to the vacuole.

Generation of free ubiquitin chains is up-regulated in stress and facilitated by the HECT domain ubiquitin ligases UFD4 and HUL5

2012 ◽  
Vol 444 (3) ◽  
pp. 611-617 ◽  
Author(s):  
Ori Braten ◽  
Nitzan Shabek ◽  
Yelena Kravtsova-Ivantsiv ◽  
Aaron Ciechanover
Keyword(s):  
Signal Transduction ◽  
Dna Damage ◽  
Ubiquitin Ligase ◽  
26S Proteasome ◽  
Specific Substrate ◽  
Polyubiquitin Chains ◽  
Hect Domain ◽  
Protein Substrate ◽  
C Terminus ◽  
Free Ubiquitin

Polyubiquitin chains serve a variety of physiological roles. Typically the chains are bound covalently to a protein substrate and in many cases target it for degradation by the 26S proteasome. However, several studies have demonstrated the existence of free polyubiquitin chains which are not linked to a specific substrate. Several physiological functions have been attributed to these chains, among them playing a role in signal transduction and serving as storage of ubiquitin for utilization under stress. In the present study, we have established a system for the detection of free ubiquitin chains and monitoring their level under changing conditions. Using this system, we show that UFD4 (ubiquitin fusion degradation 4), a HECT (homologous with E6-AP C-terminus) domain ubiquitin ligase, is involved in free chain generation. We also show that generation of these chains is stimulated in response to a variety of stresses, particularly those caused by DNA damage. However, it appears that the stress-induced synthesis of free chains is catalysed by a different ligase, HUL5 (HECT ubiquitin ligase 5), which is also a HECT domain E3.

scholarly journals Structure of the HECT domain of human WWP2

2015 ◽  
Vol 71 (10) ◽  
pp. 1251-1257 ◽  
Author(s):  
Wei Gong ◽  
Xiaodan Zhang ◽  
Wen Zhang ◽  
Jie Li ◽  
Ze Li
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Ubiquitin Ligase ◽  
Embryonic Stem ◽  
Crystallographic Analysis ◽  
Molecular Replacement ◽  
Biological Processes ◽  
Hect Domain ◽  
Ubiquitin Ligase Activity ◽  
High Degree

WWP2 is a HECT-domain ubiquitin ligase of the Nedd4 family, which is involved in various important biological processes, such as protein degradation, membrane-protein sorting and transportation, the immune response, pluripotency of embryonic stem cells, tumourigenesis and metastasis. The HECT domain provides the intrinsic ubiquitin ligase activity of WWP2. Here, the expression, purification, crystallization and crystallographic analysis of the HECT domain of human WWP2 (HECTWWP2) are reported. HECTWWP2 has been crystallized and the crystals diffracted to 2.50 Å resolution. They belonged to space group P41212 and the structure has been solved via molecular replacement. The overall structure of HECTWWP2 has an inverted T-shape. This structure displays a high degree of conservation with previously published structures of Nedd4 subfamily members.

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