Atg4a, also known as autophagy related 4A cysteine peptidase, is a core autophagy gene. During autophagy, it is involved in the deconjugation (delipidation) process, where it cleaves the isopeptide bond between LC3 or GABARAP and phosphatidylethanolamine on the autophagosome [2]. Autophagy is a crucial self-degradation pathway involved in various biological processes, and Atg4a's role in this pathway makes it biologically important. Genetic models can be used to study its function more precisely.

In human erythropoiesis, depletion of Atg4a in primary human hematopoietic stem and progenitor cells selectively impairs erythroid lineage differentiation, reducing red cell production, delaying terminal differentiation, and impairing enucleation. It also impairs autophagy and mitochondrial clearance in erythroid cells, leading to reticulocytes with retained mitochondria and autophagic vesicles [1]. In breast cancer, knockdown of Atg4a inhibits cancer progression and promotes tamoxifen chemosensitivity by suppressing autophagy [3].

In conclusion, Atg4a is essential for autophagy processes. Its role in erythroid development and breast cancer progression, as revealed through functional studies including gene knockdown models, emphasizes its significance in these biological processes and disease areas. Understanding Atg4a's function can potentially contribute to the development of new therapeutic strategies for related diseases.

References:

1. Stolla, Massiel Chavez, Reilly, Andreea, Bergantinos, Rochelle, Abkowitz, Janis L, Doulatov, Sergei. . ATG4A regulates human erythroid maturation and mitochondrial clearance. In Blood advances, 6, 3579-3589. doi:10.1182/bloodadvances.2021005910. https://pubmed.ncbi.nlm.nih.gov/35443024/

2. Nguyen, Nathan, Olivas, Taryn J, Mires, Antonio, Kauffman, Karlina J, Melia, Thomas J. 2020. The insufficiency of ATG4A in macroautophagy. In The Journal of biological chemistry, 295, 13584-13600. doi:10.1074/jbc.RA120.013897. https://pubmed.ncbi.nlm.nih.gov/32732290/

3. Li, Qingfang, Zan, Lingling. 2022. Knockdown of ATG4A inhibits breast cancer progression and promotes tamoxifen chemosensitivity by suppressing autophagy. In Molecular medicine reports, 25, . doi:10.3892/mmr.2022.12617. https://pubmed.ncbi.nlm.nih.gov/35088889/