Linear ubiquitin chain assembly complex (LUBAC) is a multi-protein complex and the only known E3 ubiquitin ligase able to conjugate ubiquitin in a head-to-tail manner to generate linear (M1-linked) polyubiquitin chains. The complex is currently known to be composed of three proteins: heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1), HOIL-1-interacting protein (HOIP), and Shank-associated RH domain-interacting protein (SHARPIN)[1],[2],.[3] HOIL-1 and HOIP are both E3 ubiquitin ligases, however, the specific linear ubiquitin-ligating activity is enacted by HOIP.[4] Mice deficient in HOIP are embryonically lethal.[5] Two cases of mutated HOIP have been detected in humans. These patients presented with autoinflammation and immunodeficiency[6],.[7] HOIL-1 is required for LUBAC assembly and stability as demonstrated by embryonic lethality in HOIL-1 deficient mice.[8] Recently, it has been noted, that HOIL-1 is also able to catalyze formation of oxyester bonds between the C-terminus of ubiquitin and serine/threonine of substrate protein in TLR signaling.[9] SHARPIN exhibits a significant sequence similarity to HOIL-1 and is important for LUBAC stability. Spontaneous point mutation in the Sharpin gene in mice leads to development of chronic proliferative dermatitis (cpdm)[10],.[11] Both HOIL-1 and SHARPIN bind to HOIP through their ubiquitin-like (UBL) domain[1],.[2] LUBAC consisting of either HOIP-HOIL-1 or HOIP-SHARPIN is functional in vitro, however the greatest activity of the complex has been observed in the presence of all three components.[2]
LUBAC modulates signaling complexes activating the canonical NF-kB pathway in response to various stimuli (e.g., TNF, IL-1, CD40L) by adding M1-linked polyubiquitin chains to signaling proteins[2],.[12] Additionally, LUBAC has been shown to interact with PKC and NLRP3/ASC inflammasome[13],.[14]
Antagonistic to LUBAC are deubiquitinases such as OTULIN or CYLD, of which OTULIN is the only deubiquitinase that removes M1-linked ubiquitin linkages exclusively.[15]
LUBAC components have been most widely studied in the context of TNF signaling.[citation needed]
^ abcdGerlach, Björn; Cordier, Stefanie M.; Schmukle, Anna C.; Emmerich, Christoph H.; Rieser, Eva; Haas, Tobias L.; Webb, Andrew I.; Rickard, James A.; Anderton, Holly; Wong, Wendy W.-L.; Nachbur, Ueli; Gangoda, Lahiru; Warnken, Uwe; Purcell, Anthony W.; Silke, John (March 2011). "Linear ubiquitination prevents inflammation and regulates immune signalling". Nature. 471 (7340): 591–596. doi:10.1038/nature09816. ISSN 1476-4687. PMID 21455173. S2CID 4384869.
^Ikeda, Fumiyo; Deribe, Yonathan Lissanu; Skånland, Sigrid S.; Stieglitz, Benjamin; Grabbe, Caroline; Franz-Wachtel, Mirita; van Wijk, Sjoerd J. L.; Goswami, Panchali; Nagy, Vanja; Terzic, Janos; Tokunaga, Fuminori; Androulidaki, Ariadne; Nakagawa, Tomoko; Pasparakis, Manolis; Iwai, Kazuhiro (March 2011). "SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis". Nature. 471 (7340): 637–641. doi:10.1038/nature09814. ISSN 1476-4687. PMC 3085511. PMID 21455181.
^Smit, Judith J; Monteferrario, Davide; Noordermeer, Sylvie M; van Dijk, Willem J; van der Reijden, Bert A; Sixma, Titia K (2012-10-03). "The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension: HOIP RBR-LDD module specifies linear ubiquitin chains". The EMBO Journal. 31 (19): 3833–3844. doi:10.1038/emboj.2012.217. PMC 3463842. PMID 22863777.
^Kelsall, Ian R.; Zhang, Jiazhen; Knebel, Axel; Arthur, J. Simon C.; Cohen, Philip (2019-07-02). "The E3 ligase HOIL-1 catalyses ester bond formation between ubiquitin and components of the Myddosome in mammalian cells". Proceedings of the National Academy of Sciences. 116 (27): 13293–13298. doi:10.1073/pnas.1905873116. ISSN 0027-8424. PMC 6613137. PMID 31209050.
^HogenEsch, H.; Torregrosa, S. E.; Boggess, D.; Sundberg, B. A.; Carroll, J.; Sundberg, J. P. (March 2001). "Increased expression of type 2 cytokines in chronic proliferative dermatitis (cpdm) mutant mice and resolution of inflammation following treatment with IL-12". European Journal of Immunology. 31 (3): 734–742. doi:10.1002/1521-4141(200103)31:3<734::aid-immu734>3.0.co;2-9. ISSN 0014-2980. PMID 11241277. S2CID 9944119.
^Seymour, R E; Hasham, M G; Cox, G A; Shultz, L D; HogenEsch, H; Roopenian, D C; Sundberg, J P (July 2007). "Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis". Genes & Immunity. 8 (5): 416–421. doi:10.1038/sj.gene.6364403. ISSN 1466-4879. PMID 17538631. S2CID 27135591.
^Rodgers, Mary A.; Bowman, James W.; Fujita, Hiroaki; Orazio, Nicole; Shi, Mude; Liang, Qiming; Amatya, Rina; Kelly, Thomas J.; Iwai, Kazuhiro; Ting, Jenny; Jung, Jae U. (2014-06-30). "The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation". Journal of Experimental Medicine. 211 (7): 1333–1347. doi:10.1084/jem.20132486. ISSN 1540-9538. PMC 4076580. PMID 24958845.
^Nakamura, Munehiro; Tokunaga, Fuminori; Sakata, Shin-ichi; Iwai, Kazuhiro (December 2006). "Mutual regulation of conventional protein kinase C and a ubiquitin ligase complex". Biochemical and Biophysical Research Communications. 351 (2): 340–347. doi:10.1016/j.bbrc.2006.09.163. PMID 17069764.
Henri-Marie Joseph Sonier de Lubac SJ (French: [lybak]; 20 February 1896 – 4 September 1991), better known as Henri de Lubac, was a French Jesuit priest...
Linear ubiquitin chain assembly complex (LUBAC) is a multi-protein complex and the only known E3 ubiquitin ligase able to conjugate ubiquitin in a head-to-tail...
Catholic theologians of the 20th century. With Joseph Ratzinger and Henri de Lubac, he founded the theological journal Communio. Over the course of his life...
Surnaturel is a book written by the Roman Catholic theologian Henri de Lubac. It stands among his most famous and controversial works. In this book he...
moyen âge was a book written by Henri de Lubac, published in Paris in 1944. The book aimed to, in de Lubac's words, retrieve the doctrine that "the Church...
Pierre Lubac (born 17 February 1968) is a French sprint canoer who competed from the late 1980s to the early 2000s (decade). Competing in four Summer...
A Fiery Serpent (also known as a snake-Lubac, Letun, Letuchy, Litavets, Maniac, nalyot, ognyanny and prelestnik) (Ukrainian: перелесник) is an evil entity...
ISBN 978-0-19-954014-3 De Lubac, Henri, The Drama of Atheist Humanism, Ignatius Press (San Francisco), 2008: pp. 74, 82. For De Lubac's full discussion of this...
1984) was a German Jesuit priest and theologian who, alongside Henri de Lubac, Hans Urs von Balthasar, and Yves Congar, is considered to be one of the...
as Maurice Blondel and fellow Jesuits, including his students Henri de Lubac, Yves de Montcheuil, and Gaston Fessard as well as Joseph Maréchal. Descoqs...
the older, more distinguished tradition of Christian thought. Henri de Lubac wrote in Surnaturel (1946), an account of Aquinas’ views on the natural...
John N.D. Kelly, Oxford University Press, 1986. Catholicism, Henri de Lubac, Ignatius Press, 1988. Rome and the Eastern Churches, Aidan Nichols, Ignatius...
founded in 1972 by Joseph Ratzinger, Hans Urs von Balthasar, Henri de Lubac, Walter Kasper, Marc Ouellet, Louis Bouyer, and others. Communio, now published...
Marie-Dominique Chenu Romano Guardini Edith Stein Fulton Sheen Henri de Lubac Dorothy Day Henri Daniel-Rops Jean Guitton Josemaría Escrivá Nouvelle théologie...
founded in 1978 by Father Joseph Fessio, a former pupil of both Henri de Lubac and Pope Benedict XVI. Named after Ignatius of Loyola, founder of the Jesuit...
death and inflammation by removing inhibitory linear ubiquitin chains from LUBAC, an enzyme that activates NF-κB. Dixit is an elected member of the National...
Marie-Dominique Chenu Romano Guardini Edith Stein Fulton Sheen Henri de Lubac Dorothy Day Henri Daniel-Rops Jean Guitton Josemaría Escrivá Nouvelle théologie...
Marie-Dominique Chenu Romano Guardini Edith Stein Fulton Sheen Henri de Lubac Dorothy Day Henri Daniel-Rops Jean Guitton Josemaría Escrivá Nouvelle théologie...
Marie-Dominique Chenu Romano Guardini Edith Stein Fulton Sheen Henri de Lubac Dorothy Day Henri Daniel-Rops Jean Guitton Josemaría Escrivá Nouvelle théologie...
forbidden to teach or to publish. Those who suffered most were the Henri de Lubac SJ and Yves Congar OP, who were unable to teach or publish until the death...