User:Bilguudei Naranbaatar

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First Draft[edit]

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Bring in 3 hard copies to class, with changes highlighted (some indication)

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Proposal[edit]

The changes all belong to 3 of the already present subheaders, Structure, Interactions, and Function. The structure section will involve a description of the various domains present in the caspase 1 protein as well as the caspase 1 interacting proteins. The important structures in caspase 1 and its interacting proteins are Caspase recruitment domains (CARDs) and Pyrin domains (PYDs).

These structures then become very important going into the next section, interactions. Here, I will discuss how the inflammasome assembles through interactions of these domains, with PYD-PYD interactions allowing a sensor protein to bind to an adaptor protein, and CARD-CARD interactions which allows the inflammasome to attach to the caspase. While this is true for many types of inflammasomes, it is not true for all, as some sensors bind directly to caspase-1, through other interactions. The CARD domains also play an important role in inhibition, where several CARD only proteins (COPs) act to repress caspase functions.[1]

Finally, I will provide detailed mechanisms for the activation of caspase 1 by the inflammasome formation, the cleavage of the IL-1beta and IL-18 precursors into mature cytokines, the cleavage of gasdermin D to induce pyroptosis, and the inhibition of caspase by the COPs.[2] I will also discuss some of the downstream effects of the mature cytokines, the various sensors that are possible in the activation of caspase 1, as well a contested topic: whether or not pyroptosis is necessary for secretion of the mature cytokines. [3]

Note: not all papers listed in the references will be necessary for these changes, but certainly more will be used than the 3 currently cited as of now.

Please let me know what other changes I could add, or any changes in structure and organization you might suggest. Thanks!

[1]References[4][5][2][6][7][8][9][3][10][11][12][13][edit]

  1. ^ a b Lu, Alvin; Li, Yang; Schmidt, Florian I.; Yin, Qian; Chen, Shuobing; Fu, Tian-Min; Tong, Alexander B.; Ploegh, Hidde L.; Mao, Youdong (2016-04-04). "Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism". Nature Structural & Molecular Biology. doi:10.1038/nsmb.3199. ISSN 1545-9985. PMID 27043298.
  2. ^ a b Samarani, Suzanne; Allam, Ossama; Sagala, Patrick; Aldabah, Zainab; Jenabian, Mohammad-Ali; Mehraj, Vikram; Tremblay, Cécile; Routy, Jean-Pierre; Amre, Devendra (2016-02-16). "Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection". Cytokine. doi:10.1016/j.cyto.2016.01.006. ISSN 1096-0023. PMID 26898120.
  3. ^ a b Vince, James E.; Silke, John (2016-04-11). "The intersection of cell death and inflammasome activation". Cellular and molecular life sciences: CMLS. doi:10.1007/s00018-016-2205-2. ISSN 1420-9071. PMID 27066895.
  4. ^ Jorgensen, Ine; Miao, Edward A. (2015-05-01). "Pyroptotic cell death defends against intracellular pathogens". Immunological Reviews. 265 (1): 130–142. doi:10.1111/imr.12287. ISSN 1600-065X. PMC 4400865. PMID 25879289.
  5. ^ Xi, Hang; Zhang, Yuling; Xu, Yanjie; Yang, William Y.; Jiang, Xiaohua; Sha, Xiaojin; Cheng, Xiaoshu; Wang, Jingfeng; Qin, Xuebin (2016-03-22). "Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells". Circulation Research. doi:10.1161/CIRCRESAHA.116.308501. ISSN 1524-4571. PMID 27006445.
  6. ^ Ainscough, Joseph S.; Gerberick, G. Frank; Kimber, Ian; Dearman, Rebecca J. (2015-12-25). "Interleukin-1β Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin". The Journal of Biological Chemistry. 290 (52): 31151–31161. doi:10.1074/jbc.M115.680694. ISSN 1083-351X. PMC 4692238. PMID 26559977.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ Rubio, Nazario; Sanz-Rodriguez, Francisco (2015-11-13). "Overexpression of caspase 1 in apoptosis-resistant astrocytes infected with the BeAn Theiler's virus". Journal of Neurovirology. doi:10.1007/s13365-015-0400-9. ISSN 1538-2443. PMID 26567013.
  8. ^ Morrison, M. C.; Mulder, P.; Salic, K.; Verheij, J.; Liang, W.; van Duyvenvoorde, W.; Menke, A.; Kooistra, T.; Kleemann, R. (2016-04-28). "Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis (NASH) and hepatic fibrosis in LDLR-/-.Leiden mice". International Journal of Obesity (2005). doi:10.1038/ijo.2016.74. ISSN 1476-5497. PMID 27121255.
  9. ^ Alvarez, Diego F.; Housley, Nicole; Koloteva, Anna; Zhou, Chun; O'Donnell, Kristen; Audia, Jonathon P. (2016-04-27). "Caspase-1 Activation Protects Lung Endothelial Barrier Function During Infection-induced Stress". American Journal of Respiratory Cell and Molecular Biology. doi:10.1165/rcmb.2015-0386OC. ISSN 1535-4989. PMID 27119735.
  10. ^ de Vasconcelos, Nathalia M.; Van Opdenbosch, Nina; Lamkanfi, Mohamed (2016-04-05). "Inflammasomes as polyvalent cell death platforms". Cellular and molecular life sciences: CMLS. doi:10.1007/s00018-016-2204-3. ISSN 1420-9071. PMID 27048821.
  11. ^ Winkler, S.; Hedrich, C. M.; Rösen-Wolff, A. (2016-04-01). "[Caspase-1 regulates autoinflammation in rheumatic diseases]". Zeitschrift Für Rheumatologie. 75 (3): 265–275. doi:10.1007/s00393-016-0077-3. ISSN 1435-1250. PMID 27034076.
  12. ^ Wallach, David; Kang, Tae-Bong; Dillon, Christopher P.; Green, Douglas R. (2016-04-01). "Programmed necrosis in inflammation: Toward identification of the effector molecules". Science (New York, N.Y.). 352 (6281): aaf2154. doi:10.1126/science.aaf2154. ISSN 1095-9203. PMID 27034377.
  13. ^ "The Inflammasome: First Line of the Immune Response to Cell Stress". {{cite journal}}: Cite journal requires |journal= (help)
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