INTERAKSI MOLEKULAR DARI RICIN-A DENGAN Beclin-1, LC3, DAN p62 PADA PROSES AUTOFAGI

Irma Erika Herawati, Ronny Lesmana, Jutti Levita, Anas Subarnas

Abstrak


Autofagi merupakan proses adaptasi yang dilakukan sebagai pertahanan dalam respon seluler, seperti kekurangan nutrisi atau stress metabolik lain. Mekanisme autofagi diregulasi oleh protein yang dinamakan Autophagy-Related Genes (ATG). Autofagi juga telah banyak dikaitkan dengan berbagai penyakit pada manusia, misalnya kanker atau penyakit degeneratif lainnya. Ricin merupakan protein toksik yang berasal dari biji jarak Ricinus communis L. dan banyak dieksplorasi untuk aktivitas antikanker melalui jalur pensinyalan caspase (apoptosis), namun belum ada penelitian pada jalur autofagi. Penelitian ini dilakukan untuk menelaah mode ikatan yang terjadi antara ricin-A dan protein-protein yang berperan pada setiap tahap proses autofagi (Beclin-1, LC3 atau Light Chain 3, dan p62/Sequistrosome1). Metode yang digunakan adalah simulasi penambatan protein-protein menggunakan server online ClusPro (https://cluspro.org). Hasil penelitian menunjukkan bahwa ricin-A dapat berinteraksi dengan Beclin-1. LC3, dan p62 melalui pembentukan ikatan hidrogen dengan afinitas baik. Dapat disimpulkan bahwa ricin-A berperan penting dalam proses autofagi dan dapat dikembangkan menjadi fitofarmaka terapi kanker.


Kata Kunci


autofagi, autophagy-related genes, Beclin-1, ricin-A, Ricinus communis L

Teks Lengkap:

DOWNLOAD (PDF)

Referensi


Herawati IE, Lesmana R, Levita J, Subarnas A. Molecular interaction of ricin-a with caspase-3, caspase-8, caspase-9 and autophagy-related gene5 (ATG5) to understand its role as anticancer agent. Rasayan J Chem. 2021;14(3).

Mizushima N, Levine B. Autophagy in human diseases. N Engl J Med. 2020;1564:76.

Lesmana R, Sinha R, Singh B, Zhou J, Ohba K. Thyroid hormone stimulation of autophagy is essential for mitochondrial biogenesis and activity in skeletal muscle. Endocrinology. 2016;157(1):23–38.

Liu E, Ryan K. Autophagy and cancer-issues we need to digest. J Cell Sci. 2012;125.

Herawati I, Levita J, Lesmana R, Subarnas A. Ricin in castor bean (Ricinus communis L.) seeds: A review on its anticancer activity and the role of cytotoxicity enhancers. Res J Pharm Technol. 2022;15. https://doi.org/10.52711/0974-360X.2022.00067

Worbs R. Apoptosis in cancer; from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30(1). Available from: https://10.0.4.162/1756-9966-30-87

Tyagi N, Tyagi M, Pachauri M, Ghosh P. Potential therapeutic applications of plant toxin-ricin in cancer: challenges and advances. Tumor Biol. 2015;36(11). Available from: https://10.0.3.239/s13277-015-4028-4

Trung N, Tho N, Dung B, Nhung Hoang T, Thang N. Effects of ricin extracted from seeds of the castor bean (Ricinus communis) on cytotoxicity and tumorigenesis of melanoma cells. Biomed Res Ther. 2016;3(5):633–44. Available from: https://10.0.29.179/s40730-016-0023-7

Lord M, Jollife N, Marsden C, Pateman C, Smith D, Spooner R, et al. Ricin. Mech Cytotox. 2003;22:53–64. Available from: https://10.0.8.117/00139709-200322010-00006

Rutenber, Katzin B, Ernst S, Collins E, Misna D, Ready M, et al. Crystallographic refinement of ricin to 2.5 A. Proteins. 1991;10.

Kozakov D, Hall R, Xia B, Porter K, Padhorny D, Yueh C, et al. The ClusPro web server for protein-protein docking. Nat Protoc. 2017;12(2). Available from: https://10.0.4.14/nprot.2016.169

Vajda S, Yueh C, Beglov D, Bohnuud T, Mottarella S, Xia B, et al. Structure, Function, and Bioinformatics. New Addit to ClusPro Serv Motiv by CAPRI. 2017;85:3. Available from: https://10.0.3.234/prot.25219

Heideman M, Johnson D, Burrus C. Gauss and the history of the Fast Fourier Transform. IEEE ASSP Mag. 1984;1(4):14–21.

Kang R, Zeh H, Lotze M, Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 2011;18(4):571–80. Available from: https://10.0.4.14/cdd.2010.191

Meijer A, Lorin S, Blommaart E, Codogno P. Regulation of autophagy by amino acids and MTOR-dependent signal transduction. Amino Acids. 2015;47(10):2037–63. Available from: https://10.0.3.239/s00726-014-1765-4

Liu W, Ye L, Huang W. p62 links the autophagy pathway and the ubiquitin–proteasome system upon ubiquitinated protein degradation. Cell Mol Biol Lett. 2016;21:29.

Li X, Haou Y, Wang X, Zhang Y, Meng X, Hu Y. To elucidate the inhibition of excessive autophagy of Rhodiola crenulata on exhaustive exercise-induced skeletal muscle injury by combined network pharmacology and molecular docking. Biol Pharm Bull. 2020;43(2):296–305. Available from: https://10.0.4.224/bpb.b19-00627

Erbil-Bilir S, Kocaturk N, Yayli M, Gozuacik D. Study of protein-protein interactions in autophagy research. J Vis. 2017;127(e):55881. Available from: https://dx.doi.org/10.3791/55881

Putyrski M, Vakhrusheva O, Bonn F, Guntur S, Vorobyov A, Brandts C, et al. Disrupting the LC3 interaction region (LIR) binding of selective autophagy receptors sensitizes AML cell lines to cytarabine. Front Cell Dev Biol. 2020;8:208.




DOI: http://dx.doi.org/10.52434/jfb.v13i1.1450

Refbacks

  • Saat ini tidak ada refbacks.


Visitor :

Web Analytics