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User:AUTOTAC

An autophagy targeting chimera (AUTOTAC) is a heterobifunctional small-molecule compound, comprising two active moieties connected by a linker, that specifically eliminates unwanted target proteins. This mode-of-action, in contrast to that of conventional enzyme inhibitors, harnesses selective intracellular proteolysis. AUTOTACs consist of two covalently-linked, protein-binding ligands: a target-binding ligand (TBL) that binds a protein-of-interest targeted for degradation, and an autophagy-targeting ligand (ATL) that engages the archetypal autophagic cargo receptor p62/SQSTM1 via its ZZ domain[1]. TBLs can include but are not limited to bind to commercial drugs, on-going and/or failed candidates, and other general ligands. ATLs comprise p62-ZZ ligands that induce p62 self-oligomerization, global autophagic flux and autophagosome biogenesis[2][3] . Thus, AUTOTACs provide a novel modality by sequestering and targeting pathological protein species to autophagic degradation. Kwon Yong-tae, a professor at Seoul National University, coined the term by establishing this concept.

Refernece

  1. ^ Cha HJ, Yu JE, Feng Z, Lee SH, Kim JG, Yang P, Han B, Sung KW, Yoo YD, Hwang JS, Terry MG, Shim SM, Song HD, Ganipisetti S, Wang N, Jang JM, Lee MJ, Kim SJ, Lee KH, Hong JT, Ciechanover A, Mook-Jung IH, Kim K, Xie XQ, Kwon YT, Kim BY (July 2019). "p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis". Nature Communications. 8 (1): 1058–1072.e9. doi:10.1038/s41467-017-00085-7. ISSN 2041-1723.
  2. ^ "The N-Degron Pathway Mediates ER-phagy". Molecular Cell. 75 (5): 1058–1072.e9. September 2019. doi:10.1016/j.molcel.2019.06.028. ISSN 1097-2765.
  3. ^ Cha HJ, Sung KS, Hwang JS, Kim KA, Yu JE, Yoo YD, Jang JM, Han DH, Molstad M, Kim JG, Lee YJ, Zakrzewska A, Kim SH, Kim ST, Kim SY, Lee HG, Soung NK, Ahn JS, Ciechanover A, Kim BY, Kwon YT (July 2015). "Amino-terminal arginylation targets endoplasmic reticulum chaperone BiP for autophagy through p62 binding". Nature Cell Biology. 17 (7): 917–929. doi:10.1038/ncb3177. ISSN 1476-4679. PMC 4490096. PMID 26075355.{{cite journal}}: CS1 maint: PMC format (link)

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