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AKT Phosphorylates FAM13A and Promotes Its Degradation via CUL4A/DDB1/DCAF1 E3 Complex

Lu Gong1,2, Samuel Bates1,2, Yujun Li1,2

  • 1Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

American Journal of Respiratory Cell and Molecular Biology
|February 7, 2023
PubMed

Insights

Researchers discovered how AKT kinase regulates FAM13A protein stability via phosphorylation and ubiquitination, impacting lung epithelial repair after injury. This finding is crucial for understanding chronic obstructive pulmonary disease.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Pulmonary Medicine

Background:

  • Single nucleotide polymorphisms (SNPs) in the FAM13A gene are linked to chronic obstructive pulmonary disease (COPD) and lung function.
  • The regulation of FAM13A protein under physiological and pathological conditions is not well understood.

Purpose of the Study:

  • To elucidate the regulatory mechanisms governing FAM13A protein stability.
  • To investigate the functional role of FAM13A regulation in lung epithelial repair.

Main Methods:

  • Treatment of cells with cigarette smoke extract.
  • Analysis of FAM13A phosphorylation and ubiquitination.
  • In vivo studies using mouse models of lung injury (influenza, naphthalene).
  • Assessment of epithelial cell proliferation during lung repair.

Main Results:

  • FAM13A is phosphorylated at serine 312 by AKT kinase upon cigarette smoke extract treatment.
  • Phosphorylated FAM13A is recognized and degraded by the CULLIN4A/DCAF1 E3 ligase complex.
  • FAM13A protein is downregulated upon AKT activation in stressed and injured mouse lungs.
  • Reduced FAM13A levels promote accelerated lung epithelial cell proliferation during repair.

Conclusions:

  • A novel mechanism for FAM13A protein regulation via ubiquitination-mediated degradation has been characterized.
  • This regulatory pathway fine-tunes lung epithelial repair following injury.
  • Understanding FAM13A regulation may offer insights into COPD and other lung diseases.
Keywords:
AKTE3 ligaseFAM13Acellular responseprotein degradation

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