ATG4B (human recombinant)

Autophagy-related 4B (ATG4B), also known as autophagin-1, is a cysteine protease and a member of the C54 protease family with dual roles in the progression of autophagy.^1,2 It catalyzes the irreversible proteolytic cleavage of human homologs of yeast atg8 belonging to the microtubule-associated proteins 1 (MAP1)A/B-light chain 3 (LC3) and the GABA receptor-associated protein (GABARAP) subfamilies, including LC3, GATE16, GABARAP, and ATG8L, to expose a C-terminal glycine residue that is essential to formation of the autophagosome. It also catalyzes the reversible deconjugation of phosphatidylethanolamine from C-terminal glycine lipid-conjugated atg8 homologs.³ ATG4B expression is increased in CD34⁺ chronic myeloid leukemia (CML) stem and progenitor cells and knockdown of ATG4B expression increases accumulation of LC3-II and p62, indicating impaired autophagy, and reduces the viability and inhibits proliferation of CD34⁺ CML cells.⁴ Atg4^-/- mice exhibit systemic decreases in basal and induced autophagy as well as increased susceptibility to colitis induced by dextran sodium sulfate (DSS) and pulmonary fibrosis induced by bleomycin (Item No. 13877).^5,6

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1. Li, M., Hou, Y., Wang, J., et al. Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. The Journal of Biological Chemisty 286(9), 7327-7338 (2011).

2. Yang, Z., Wilkie-Grantham, R.P., Yanagi, T., et al. ATG4B (Autophagin-1) phosphorylation modulates autophagy. The Journal of Biological Chemisty 290(44), 26549-26561 (2015).

3. Kabeya, Y., Mizushima, N., Yamamoto, A., et al. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 117(Pt 13), 2805-2812 (2004).

4. Rothe, K., Lin, H., Lin, K.B., et al. The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood 123(23), 3622-3634 (2014).

5. Cabrera, S., Fernández, A.F., Mariño, G., et al. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis. Autophagy 9(8), 1188-1200 (2013).

6. Cabrera, S., Maciel, M., Herrera, I., et al. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis. Autophagy 11(4), 670-684 (2015).