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However, how FAM13A protein is regulated under physiological and pathological conditions remains largely elusive. Herein, we report that FAM13A is phosphorylated at the serine 312 residue by AKT kinase after cigarette smoke extract treatment and thereby recognized by the CULLIN4A\/DCAF1 (DDB1 and CUL4 associated factor 1) E3 ligase complex, rendering the ubiquitination-mediated degradation of FAM13A. More broadly, downregulation of FAM13A protein upon AKT activation, as a general cellular response to acute stress, was also detected in influenza- or naphthalene-injured lungs in mice. Functionally, reduced protein levels of FAM13A lead to accelerated epithelial cell proliferation in murine lungs during the recovery phase after injury. In summary, we characterized a novel molecular mechanism that regulates the stability of FAM13A protein, which enables the fine-tuning of lung epithelial repair after injury. These significant findings will expand our molecular understanding of the regulation of protein stability, which may modulate lung epithelial repair implicated in the development of chronic obstructive pulmonary disease and other lung diseases.<\/jats:p>","DOI":"10.1165\/rcmb.2022-0362oc","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T11:22:37Z","timestamp":1675768957000},"page":"577-590","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":8,"title":["AKT Phosphorylates FAM13A and Promotes Its Degradation via CUL4A\/DDB1\/DCAF1 E3 Complex"],"prefix":"10.1093","volume":"68","author":[{"given":"Lu","family":"Gong","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts; 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