adducin 1 is essential for the survival of erythroid precursors via regulating p53 transcription in zebrafish
Shuyan Yang,
Shanhu Cao,
Xuebing Xu,
Quan Li,
Jianting Li,
Jin Guo,
Fang Wang,
Yihua Bao,
Zean Jiang,
Ting Zhang,
Li Wang,
Shaoguang Sun
Affiliations
Shuyan Yang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Corresponding author
Shanhu Cao
Department of Biochemistry and Molecular Biology, Key Laboratory of Medical Biotechnology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang 050017, China
Xuebing Xu
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Affiliated Hospital of Weifang Medical University, School of Clinical Medicine, Weifang Medical University, Weifang, China
Quan Li
Beijing Institutes of Life Science Chinese Academy of Sciences, Beijing 100101, China
Jianting Li
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
Jin Guo
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Fang Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Yihua Bao
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Zean Jiang
Department of Biochemistry and Molecular Biology, Key Laboratory of Medical Biotechnology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang 050017, China
Ting Zhang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Li Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Corresponding author
Shaoguang Sun
Department of Biochemistry and Molecular Biology, Key Laboratory of Medical Biotechnology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang 050017, China; Corresponding author
Summary: Adducin 1 (Add1) is known as a membrane cytoskeletal protein, but its nuclear function remains unclear. In this study, we generated add1-deficient zebrafish to investigate its role in hematopoiesis. Lack of add1 impaired both primitive and definitive hematopoiesis, preventing healthy erythrocyte development. RNA sequencing revealed activation of the p53 pathway in add1-depleted erythroblast cells, leading to apoptosis at the 14-somites stage and 24 hpf. Interestingly, partial rescue of the anemic phenotype and apoptosis was observed with p53 insufficiency. Mechanistically, ADD1 was found to regulate promoter activity. These findings demonstrate that Add1 plays a crucial role in zebrafish erythropoiesis, involving the p53-mediated apoptotic pathway, expanding its regulatory role beyond cytoskeletal functions.
