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Keywords: ubiquitin
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Articles
Biochem J (2022) 479 (9): 929–951.
Published: 06 May 2022
...-translational modifications in control of its function. Ubiquitination by E3 ligases, such as inhibitors of apoptosis (IAP) proteins and LUBAC, as well as the reversal of these modifications by deubiquitinating enzymes, such as A20 and CYLD, can greatly influence RIP1 mediated signaling. In addition, cleavage...
Articles
Biochem J (2022) 479 (6): 751–766.
Published: 28 March 2022
...Karen M. Dunkerley; Anne C. Rintala-Dempsey; Giulia Salzano; Roya Tadayon; Dania Hadi; Kathryn R. Barber; Helen Walden; Gary S. Shaw The RBR E3 ligase parkin is recruited to the outer mitochondrial membrane (OMM) during oxidative stress where it becomes activated and ubiquitinates numerous proteins...
Includes: Supplementary data
Articles
Biochem J (2021) 478 (13): 2517–2531.
Published: 02 July 2021
... generates viral non-structural proteins from a polyprotein precursor, and cleaves ubiquitin and ISG protein conjugates. Here we describe the expression and purification of PLpro. We developed a protease assay that was used to screen a custom compound library from which we identified dihydrotanshinone I...
Includes: Supplementary data
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Biochem J (2019) 476 (14): 2127–2139.
Published: 31 July 2019
...Bing Liu; L. Maria Lois; David Reverter SUMOylation of proteins involves the concerted action of the E1-activating enzyme, E2-conjugating enzyme and E3-ligases. An essential discrimination step in the SUMOylation pathway corresponds to the initial interaction between E1 ubiquitin-fold domain (UFD...
Articles
Biochem J (2017) 474 (13): 2235–2248.
Published: 26 June 2017
...Jiazhen Zhang; Thomas Macartney; Mark Peggie; Philip Cohen Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin (K63-Ub) chains, which are thought to activate the ‘master’ protein kinase TGFβ-activated kinase 1 (TAK1) by interacting with its TAK1-binding 2 (TAB2) and TAB3...
Includes: Supplementary data
Articles
Biochem J (2017) 474 (13): 2177–2190.
Published: 16 June 2017
...Klementina Fon Tacer; Patrick Ryan Potts Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader–Willi Syndrome (PWS) and Schaaf–Yang...
Articles
Biochem J (2017) 474 (9): 1439–1451.
Published: 13 April 2017
... regulation of protein quality control pathways with a consequent increase in protein misfolding and aggregation and failure of the protein degradation machinery. Ubiquitin signalling plays a central role in protein quality control; however, prior to genetic advances, the detailed mechanisms of how impairment...
Articles
Biochem J (2017) 474 (7): 1163–1174.
Published: 15 March 2017
... at Ser396 and production of IFNβ were greatly reduced in bone marrow-derived macrophages (BMDMs) from TANK knockout (KO) mice crossed to knockin mice expressing the ubiquitin-binding-defective OPTN[D477N] mutant. In contrast, IRF3 phosphorylation and IFNβ production were not reduced significantly in BMDM...
Includes: Supplementary data
Articles
Biochem J (2016) 473 (24): 4551–4558.
Published: 09 December 2016
... polyamine uptake. Az acts as a sensor of the free intracellular polyamine pools as it is expressed via a polyamine-stimulated ribosomal frameshifting. Az binds to monomeric ODC subunits to prevent their reassociation into active homodimers and facilitates their ubiquitin-independent degradation by the 26S...
Articles
Biochem J (2016) 473 (24): 4507–4525.
Published: 09 December 2016
...Aidan P. McCann; Christopher J. Scott; Sandra Van Schaeybroeck; James F. Burrows In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has...
Articles
Biochem J (2016) 473 (22): 4083–4101.
Published: 10 November 2016
... of the ubiquitin proteasome system (UPS), determining the substrate specificity of the cascade by the covalent attachment of ubiquitin to substrate proteins. Currently, there are over 600 putative E3 ligases, but many are poorly characterized, particularly with respect to individual protein substrates. Here, we...
Articles
Biochem J (2016) 473 (10): 1297–1314.
Published: 11 May 2016
...Mathew Stanley; Satpal Virdee The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from...
Articles
Biochem J (2016) 473 (2): e5–e8.
Published: 05 January 2016
...Philip Woodman The multivesicular body (MVB) pathway sorts ubiquitinated membrane cargo to intraluminal vesicles (ILVs) within the endosome, en route to the lysosomal lumen. The pathway involves the sequential action of conserved protein complexes [endosomal sorting complexes required for transport...
Articles
Biochem J (2015) 472 (3): 353–365.
Published: 27 November 2015
.... Interestingly, Rpn10–ubiquitin, with an inactivated ubiquitin-interacting motif (UIM), and Dsk2 I45S , with an inactive ubiquitin-like domain (UBL), show temperature-dependent phenotypes with multiple functional interactions. 1 These authors contributed equally to the study. 2 To whom...
Includes: Supplementary data
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Biochem J (2015) 470 (3): e21–e24.
Published: 04 September 2015
...-knockout and LRRK2 kinase-dead rodent models. In a recent issue of the Biochemical Journal , a study led by Nichols reveals that dephosphorylation of LRRK2 cellular phosphorylation sites (Ser 910 /Ser 935 /Ser 955 /Ser 973 ) triggers its ubiquitination and subsequent degradation and thus may account...
Articles
Biochem J (2015) 469 (3): 455–467.
Published: 23 July 2015
...-phenotype protein 5) and this modification impairs the interaction of Rpn10 with substrates, having a regulatory effect on proteasome function. Remarkably, a disordered region near the ubiquitin-interacting motif of Rpn10 plays a role in the restriction of the polyubiquitin extension activity of Rsp5...
Includes: Supplementary data
Articles
Biochem J (2015) 469 (1): 107–120.
Published: 19 June 2015
... for inhibited LRRK2. Loss of 14-3-3 binding is well established, but the consequences of dephosphorylation are only now being uncovered. In the present study, we found that potent and selective inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser 935 then ubiquitination and degradation...
Articles
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Biochem J (2015) 468 (2): 215–226.
Published: 22 May 2015
...Miklós Békés; Wioletta Rut; Paulina Kasperkiewicz; Monique P.C. Mulder; Huib Ovaa; Marcin Drag; Christopher D. Lima; Tony T. Huang Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15 (ISG15) participate in the host defence of viral infections. Viruses, including the severe...
Includes: Supplementary data
Articles
Biochem J (2015) 467 (3): 365–386.
Published: 17 April 2015
...Emil Bulatov; Alessio Ciulli In the last decade, the ubiquitin–proteasome system has emerged as a valid target for the development of novel therapeutics. E3 ubiquitin ligases are particularly attractive targets because they confer substrate specificity on the ubiquitin system. CRLs [Cullin–RING...
Includes: Supplementary data
Articles
Biochem J (2015) 466 (3): 489–498.
Published: 06 March 2015
...John S. Bett; Maria Stella Ritorto; Richard Ewan; Ellis G. Jaffray; Satpal Virdee; Jason W. Chin; Axel Knebel; Thimo Kurz; Matthias Trost; Michael H. Tatham; Ronald T. Hay Modification of proteins with ubiquitin (Ub) occurs through a variety of topologically distinct Ub linkages, including Ube2W...
Includes: Supplementary data
Articles
Biochem J (2015) 466 (1): 45–54.
Published: 06 February 2015
... and represents a fundamental challenge to sustaining clinical efficacy for currently available agents. Inhibitor of apoptosis (IAP) proteins use their ubiquitin E3 ligase activity to promote cancer cell survival by mediating proliferative signalling and blocking cell death in response to diverse stimuli. Using...
Includes: Supplementary data
Articles
Biochem J (2015) 465 (1): 1–26.
Published: 12 December 2014
...Johanna Heideker; Ingrid E. Wertz The post-translational modification of proteins with ubiquitin represents a complex signalling system that co-ordinates essential cellular functions, including proteolysis, DNA repair, receptor signalling and cell communication. DUBs (deubiquitinases), the enzymes...
Articles
Biochem J (2014) 463 (1): 65–74.
Published: 08 September 2014
...-defective phenotype of peroxisome biogenesis disorders. The mechanisms by which the protein level and quality of Pex7p are controlled remain largely unknown. In the present study we show that dysfunctional Pex7p, including mutants from RCDP patients, is degraded by a ubiquitin-dependent proteasomal pathway...
Includes: Supplementary data
Articles
Biochem J (2014) 460 (2): 237–246.
Published: 13 May 2014
... isoforms are controlled by a Cullin-RING E3 ubiquitin ligase complex (CRL3 KLHL3 ) that utilizes CUL3 (Cullin3) and its substrate adaptor, KLHL3 (Kelch-like protein 3). Loss-of-function mutations in either CUL3 or KLHL3 cause the hereditary high blood pressure disease Gordon's syndrome by stabilizing WNK...
Includes: Supplementary data
Articles
Biochem J (2014) 460 (1): 127–141.
Published: 25 April 2014
...) is activated by mitochondrial depolarization and stimulates the Parkin E3 ligase by phosphorylating Ser 65 within its Ubl (ubiquitin-like) domain. Using phosphoproteomic analysis, we identified a novel ubiquitin phosphopeptide phosphorylated at Ser 65 that was enriched 14-fold in HEK (human embryonic kidney...
Includes: Supplementary data
Articles
Biochem J (2014) 459 (1): 205–216.
Published: 14 March 2014
... this process, p97 binds polyubiquitinated ERAD substrates and couples ATP hydrolysis to their dislocation from the ER as a prerequisite to destruction by the proteasome. The ubiquitin signals important for this process are not fully understood. In the present paper we report that p97 interacts with Lys 11...
Articles
Biochem J (2014) 458 (3): 459–467.
Published: 28 February 2014
... is mediated by ubiquitin conjugation. After modification with ubiquitin, substrates are escorted to the proteasome by myriad factors, including Cdc48 (cell-division cycle 48). Cdc48 also associates with numerous cofactors, but, to date, it is unclear whether each cofactor facilitates proteasome delivery. We...
Includes: Supplementary data
Articles
Biochem J (2014) 457 (3): 435–440.
Published: 10 January 2014
...Joanne L. Parker; Helle D. Ulrich SIMs (SUMO-interaction motifs), which mediate the non-covalent binding of SUMO (small ubiquitin-related modifier) to other proteins, are usually involved in the recognition of SUMOylated substrates by downstream effectors that transmit the biological signal...
Articles
Biochem J (2014) 457 (2): 289–300.
Published: 20 December 2013
... and producing an N-terminally truncated protein. We demonstrate that both RCE1 isoform 1 and the newly identified isoform 2 are required to reinstate proper H-Ras processing and thus plasma membrane localization in RCE1-null cells. In addition, we show that the deubiquitinating enzyme USP17 (ubiquitin-specific...
Includes: Supplementary data
Articles
Biochem J (2013) 453 (1): 137–145.
Published: 13 June 2013
...Michael H. Tatham; Anna Plechanovová; Ellis G. Jaffray; Helena Salmen; Ronald T. Hay The covalent attachment of the protein ubiquitin to intracellular proteins by a process known as ubiquitylation regulates almost all major cellular systems, predominantly by regulating protein turnover...
Includes: Supplementary data
Articles
Biochem J (2013) 451 (1): 111–122.
Published: 14 March 2013
... to form Cullin–RING E3 ubiquitin ligase complexes. To explore how a CUL3–KLHL3 complex might operate, we immunoprecipitated KLHL3 and found that it associated strongly with WNK isoforms and CUL3, but not with other components of the pathway [SPAK/OSR1 or NCC (Na + /Cl − co-transporter)/NKCC1 (Na + /K...
Includes: Supplementary data
Articles
Biochem J (2013) 450 (3): 629–638.
Published: 28 February 2013
...Yoshio Nakatani; Torsten Kleffmann; Katrin Linke; Stephen M. Condon; Mark G. Hinds; Catherine L. Day RING domains of E3 ligases promote transfer of Ub (ubiquitin) from the E2~Ub conjugate to target proteins. In many cases interaction of the E2~Ub conjugate with the RING domain requires its prior...
Includes: Supplementary data
Articles
Biochem J (2012) 448 (1): 55–65.
Published: 18 October 2012
...Jonas Boehringer; Christiane Riedinger; Konstantinos Paraskevopoulos; Eachan O. D. Johnson; Edward D. Lowe; Christina Khoudian; Dominique Smith; Martin E. M. Noble; Colin Gordon; Jane A. Endicott The ubiquitin–proteasome system targets selected proteins for degradation by the 26S proteasome. Rpn12...
Includes: Supplementary data
Articles
Biochem J (2012) 445 (2): 167–174.
Published: 27 June 2012
...Benjamin W. Cook; Gary S. Shaw E2 conjugating enzymes are the central enzymes in the ubiquitination pathway and are responsible for the transfer of ubiquitin and ubiquitin-like proteins on to target substrates. The secondary structural elements of the catalytic domain of these enzymes is highly...
Includes: Supplementary data
Articles
Biochem J (2012) 442 (1): 13–25.
Published: 27 January 2012
... attachment of a full-length protein such as ubiquitin. The protein ubiquitylation machinery is remarkably complex, comprising more than 15 Ubls (ubiquitin-like proteins) and several hundreds of ubiquitin-conjugating enzymes. Ubiquitin is best known for its role as a tag that induces protein destruction...
Articles
Biochem J (2011) 435 (3): 641–649.
Published: 13 April 2011
...Mei Kee Lim; Wee Leng Siew; Jin Zhao; Ywee Chieh Tay; Edwin Ang; Norbert Lehming Skp1 an essential component of the SCF (Skp1/cullin/F-box) E3 ubiquitin ligases, which target proteins for degradation by the 26S proteasome. We generated a skp1dM mutant strain that is defective for galactose...
Includes: Supplementary data
Articles
Biochem J (2011) 435 (2): 509–518.
Published: 29 March 2011
... modifications. Overexpressed 5KR EPO-R displayed impaired ubiquitination and improved stability compared with wt (wild-type) EPO-R. Unexpectedly, fusion proteins consisting of VSVGtsO45 (vesicular stomatitis virus glycoprotein temperature-sensitive folding mutant) with wt or 5KR EPO-R cytosolic domains...
Articles
Biochem J (2011) 434 (3): 537–548.
Published: 24 February 2011
... (interleukin receptor associated kinase) 1/IRAK4 in vitro , converting them into active E3 ubiquitin ligases. In the present paper we report a striking enhancement in both transcription of the gene encoding Pellino 1 and Pellino 1 protein expression when murine BMDMs (bone-marrow-derived macrophages...
Includes: Supplementary data
Articles
Biochem J (2010) 431 (3): 391–402.
Published: 11 October 2010
..., we found that the overexpression of the de-ubiquitinating enzyme Ubp3 (ubiquitin-specific protease 3) also stabilizes the Tbp1E186D mutant protein and suppresses of the defects of the TBP1E186D mutant strain. Importantly, the deletion of UBP3 and its cofactor BRE5 lead to increased degradation...
Includes: Supplementary data
Articles
Biochem J (2010) 431 (1): 23–29.
Published: 14 September 2010
...Chu Wai Liew; Huaiyu Sun; Tony Hunter; Catherine L. Day RNF4 [RING (really interesting new gene) finger protein 4] family ubiquitin ligases are RING E3 ligases that regulate the homoeostasis of SUMOylated proteins by promoting their ubiquitylation. In the present paper we report that the RING...
Includes: Supplementary data
Articles
Biochem J (2010) 428 (2): 133–145.
Published: 13 May 2010
...Kevin A. Wilkinson; Jeremy M. Henley The post-translational modification SUMOylation is a major regulator of protein function that plays an important role in a wide range of cellular processes. SUMOylation involves the covalent attachment of a member of the SUMO (small ubiquitin-like modifier...
Articles
Biochem J (2009) 423 (3): 375–380.
Published: 12 October 2009
... for ubiquitin revealed a dramatic increase in the ubiquitin content of Tie2 in cells stimulated with Ang1 ( Figure 1 ; αUb). The levels of ubiquitin incorporation did appear marginally different between the two cell types. Whether this reflects differences in levels of Tie2 expression or the extent...
Articles
Biochem J (2009) 422 (2): 207–215.
Published: 13 August 2009
...Shanhui Liao; Qiang Shang; Xuecheng Zhang; Jiahai Zhang; Chao Xu; Xiaoming Tu Pup (prokaryotic ubiquitin-like protein) from Mycobacterium tuberculosis is the first ubiquitin-like protein identified in non-eukaryotic cells. Although different ubiquitin-like proteins from eukaryotes share low...
Includes: Supplementary data
Articles
Biochem J (2009) 421 (3): 397–404.
Published: 15 July 2009
... disparate effects on rates of ATP hydrolysis. The effect of polyubiquitin was specific for ubiquitinubiquitin linkages that supported proteolysis of protein substrates. These results indicate that gating of the 26S proteasome is not a simple two-state process but can be variably modulated. Our results...
Articles
Biochem J (2009) 421 (2): 243–251.
Published: 26 June 2009
...-ubiquitin with a stoichiometry of one molecule of di-ubiquitin per NEMO dimer. This stoichiometry is preserved in a construct comprising the second coiled-coil region and the leucine zipper and in one that essentially spans the full-length protein. However, our data show that at high di-ubiquitin...
Articles
Biochem J (2009) 421 (2): 223–230.
Published: 26 June 2009
...Lin Nan Shen; Marie-Claude Geoffroy; Ellis G. Jaffray; Ronald T. Hay The modification of proteins by SUMO ( s mall u biquitin-related mo difier) plays important roles in regulating the activity, stability and cellular localization of target proteins. Similar to ubiquitination, SUMO modification...
Articles
Biochem J (2009) 418 (2): 379–390.
Published: 11 February 2009
.... Biochemical analysis reveals that OTUB1 has a preference for cleaving Lys 48 -linked polyubiquitin chains over Lys 63 -linked polyubiquitin chains, and it is capable of cleaving NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8), but not SUMO (small ubiquitin-related modifier) 1/2/3...
Includes: Supplementary data
Articles
Biochem J (2009) 417 (2): 601–609.
Published: 23 December 2008
... homoeostasis, sodium transport and adaptation to hypoxia. The best-studied member of this family is COMMD1, but relatively little is known about its regulation, except that XIAP [X-linked IAP (inhibitor of apoptosis)] functions as its ubiquitin ligase. In the present study, we identified that the COMM domain...
Articles
Biochem J (2009) 417 (1): 149–165.
Published: 12 December 2008
... (nuclear factor κB) activation. Additionally, through their E3 ubiquitin ligase activities, c-IAP1 and c-IAP2 promote proteasomal degradation of NIK (NF-κB-inducing kinase) and regulate the non-canonical NF-κB pathway. In the present paper, we describe a novel ubiquitin-binding domain of IAPs. The UBA...
Includes: Supplementary data
Articles
Biochem J (2009) 417 (1): e1–e3.
Published: 12 December 2008
...Krishnaraj Rajalingam; Ivan Dikic IAP (inhibitor of apoptosis) proteins are a class of anti-apoptotic regulators characterized by the presence of BIR (baculoviral IAP repeat) domains. Some of the IAPs also possess a RING (really interesting new gene) domain with E3 ubiquitin ligase activity...