scholarly journals ER-embedded UBE2J1/RNF26 ubiquitylation complex in spatiotemporal control of the endolysosomal pathway

2020 ◽  
Author(s):  
Tom Cremer ◽  
Marlieke L.M. Jongsma ◽  
Fredrik Trulsson ◽  
Alfred C.O. Vertegaal ◽  
Jacques J.C. Neefjes ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Cell Periphery ◽  
Perinuclear Region ◽  
Cellular Activity ◽  
Cellular Functions ◽  
Transport Dynamics ◽  
Ubiquitin Conjugating Enzyme ◽  
Spatiotemporal Control ◽  
Conjugating Enzyme

AbstractThe endolysosomal system fulfills a wide variety of cellular functions, many of which are modulated through interactions with other organelles. In particular, the ER exerts spatiotemporal constraints on the organization and motility of endosomes and lysosomes. We have recently described the ER transmembrane E3 ubiquitin ligase RNF26 to control perinuclear positioning and transport dynamics of the endolysosomal vesicular network. We now report that the ubiquitin conjugating enzyme UBE2J1, also anchored in the ER membrane, collaborates with RNF26 in this context, and that the cellular activity of this E2/E3 pair, localized in a perinuclear ER subdomain, is underpinned by transmembrane interactions. Through modification of its substrate SQSTM1/p62, the ER-embedded UBE2J1/RNF26 ubiquitylation complex recruits endosomal adaptors to immobilize their cognate vesicles in the perinuclear region. The resulting spatiotemporal compartmentalization of the endolysosomal system between the perinuclear vesicle cloud and the cell periphery facilitates timely downregulation of endocytosed cargoes, such as EGFR.

DNA Damage-Induced Foci of E2 Ubiquitin-Conjugating Enzyme are Detectable upon Co-transfection with an Interacting E3 Ubiquitin Ligase

2015 ◽  
Vol 54 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Degui Wang ◽  
Yingxia Tian ◽  
Dong Wei ◽  
Yuhong Jing ◽  
Haitao Niu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

scholarly journals In Vivo Action of the HRD Ubiquitin Ligase Complex: Mechanisms of Endoplasmic Reticulum Quality Control and Sterol Regulation

2001 ◽  
Vol 21 (13) ◽  
pp. 4276-4291 ◽  
Author(s):  
Richard G. Gardner ◽  
Alexander G. Shearer ◽  
Randolph Y. Hampton
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Ubiquitin Ligase ◽  
Sequence Similarity ◽  
High Specificity ◽  
Specific Sequence ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

ABSTRACT Ubiquitination is used to target both normal proteins for specific regulated degradation and misfolded proteins for purposes of quality control destruction. Ubiquitin ligases, or E3 proteins, promote ubiquitination by effecting the specific transfer of ubiquitin from the correct ubiquitin-conjugating enzyme, or E2 protein, to the target substrate. Substrate specificity is usually determined by specific sequence determinants, or degrons, in the target substrate that are recognized by the ubiquitin ligase. In quality control, however, a potentially vast collection of proteins with characteristic hallmarks of misfolding or misassembly are targeted with high specificity despite the lack of any sequence similarity between substrates. In order to understand the mechanisms of quality control ubiquitination, we have focused our attention on the first characterized quality control ubiquitin ligase, the HRD complex, which is responsible for the endoplasmic reticulum (ER)-associated degradation (ERAD) of numerous ER-resident proteins. Using an in vivo cross-linking assay, we directly examined the association of the separate HRDcomplex components with various ERAD substrates. We have discovered that the HRD ubiquitin ligase complex associates with both ERAD substrates and stable proteins, but only mediates ubiquitin-conjugating enzyme association with ERAD substrates. Our studies with the sterol pathway-regulated ERAD substrate Hmg2p, an isozyme of the yeast cholesterol biosynthetic enzyme HMG-coenzyme A reductase (HMGR), indicated that the HRD complex discerns between a degradation-competent “misfolded” state and a stable, tightly folded state. Thus, it appears that the physiologically regulated, HRD-dependent degradation of HMGR is effected by a programmed structural transition from a stable protein to a quality control substrate.

scholarly journals Antagonistic Regulation of Circadian Output and Synaptic Development by the E3 Ubiquitin Ligase JETLAG and the DYSCHRONIC-SLOWPOKE Complex

2019 ◽  
Author(s):  
Angelique Lamaze ◽  
James E.C Jepson ◽  
Oghenerukevwe Akpoghiran ◽  
Kyunghee Koh
Keyword(s):  
Neuromuscular Junction ◽  
Ubiquitin Ligase ◽  
Light Exposure ◽  
E3 Ubiquitin Ligase ◽  
List Type ◽  
Cellular Functions ◽  
Synaptic Development ◽  
Channel Expression ◽  
Pdz Protein ◽  
Larval Neuromuscular Junction

SummaryCircadian output genes act downstream of the clock to promote rhythmic changes in behavior and physiology, yet their molecular and cellular functions are not well understood. Here we characterize an interaction between regulators of circadian entrainment, output and synaptic development in Drosophila that influences clock-driven anticipatory increases in morning and evening activity. We previously showed the JETLAG (JET) E3 Ubiquitin ligase resets the clock upon light exposure, while the PDZ protein DYSCHRONIC (DYSC) regulates circadian locomotor output and synaptic development. Surprisingly, we find that JET and DYSC antagonistically regulate synaptic development at the larval neuromuscular junction, and reduced JET activity rescues arrhythmicity of dysc mutants. Consistent with our prior finding that DYSC regulates SLOWPOKE (SLO) potassium channel expression, jet mutations also rescue circadian and synaptic phenotypes in slo mutants. Collectively, our data suggest that JET, DYSC and SLO promote circadian output in part by regulating synaptic morphology.HighlightsLoss of DYSC differentially impacts morning and evening oscillatorsReduced JET activity rescues the dysc and slo arrhythmic phenotypeReduced JET activity causes synaptic defects at the larval NMJJET opposes DYSC and SLO function at the NMJ synapse

scholarly journals Noncanonical E2 Variant-Independent Function of UBC13 in Promoting Checkpoint Protein Assembly

2008 ◽  
Vol 28 (19) ◽  
pp. 6104-6112 ◽  
Author(s):  
Michael S. Y. Huen ◽  
Jun Huang ◽  
Jingsong Yuan ◽  
Masahiro Yamamoto ◽  
Shizuo Akira ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Protein Assembly ◽  
Ring Domain ◽  
Dna Breaks ◽  
Focus Formation ◽  
Checkpoint Protein ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Conjugating Enzyme

ABSTRACT The E2 ubiquitin-conjugating enzyme UBC13 plays pivotal roles in diverse biological processes. Recent studies have elucidated that UBC13, in concert with the E3 ubiquitin ligase RNF8, propagates the DNA damage signal via a ubiquitylation-dependent signaling pathway. However, mechanistically how UBC13 mediates its role in promoting checkpoint protein assembly and its genetic requirement for E2 variants remain elusive. Here we provide evidence to support the idea that the E3 ubiquitin ligase complex RNF8-UBC13 functions independently of E2 variants and is sufficient in facilitating ubiquitin conjugations and accumulation of DNA damage mediator 53BP1 at DNA breaks. The RNF8 RING domain serves as the molecular platform to anchor UBC13 at the damaged chromatin, where localized ubiquitylation events allow sustained accumulation of checkpoint proteins. Intriguingly, we found that only a group of RING domains derived from E3 ubiquitin ligases, which have been shown to interact with UBC13, enabled UBC13-mediated FK2 and 53BP1 focus formation at DNA breaks. We propose that the RNF8 RING domain selects and loads a subset of UBC13 molecules, distinct from those that exist as heterodimers, onto sites of double-strand breaks, which facilitates the amplification of DNA damage signals.

scholarly journals Features of the Parkin/Ariadne-like Ubiquitin Ligase, HHARI, That Regulate Its Interaction with the Ubiquitin-conjugating Enzyme, UbcH7

2001 ◽  
Vol 276 (22) ◽  
pp. 19640-19647 ◽  
Author(s):  
Helen C. Ardley ◽  
Nancy G. S. Tan ◽  
Stephen A. Rose ◽  
Alexander F. Markham ◽  
Philip A. Robinson
Keyword(s):  
Ubiquitin Ligase ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

scholarly journals E2 Conjugating Enzyme Selectivity and Requirements for Function of the E3 Ubiquitin Ligase CHIP

2011 ◽  
Vol 286 (24) ◽  
pp. 21277-21286 ◽  
Author(s):  
Sarah E. Soss ◽  
Yuanyuan Yue ◽  
Sirano Dhe-Paganon ◽  
Walter J. Chazin
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Enzyme Selectivity ◽  
Conjugating Enzyme
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