2. Academic Validation
  3. SOSSB1 and SOSSB2 mutually regulate protein stability through competitive binding of SOSSA

SOSSB1 and SOSSB2 mutually regulate protein stability through competitive binding of SOSSA

  • Cell Death Discov. 2023 Aug 28;9(1):319. doi: 10.1038/s41420-023-01619-3.
Qi Zhang 1,  Rongjiao Hao 2,  Hongxia Chen 3,  Gangqiao Zhou 4 5 6 7
Affiliations

Affiliations

  • 1 Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, 421001, P.R. China.
  • 2 School of Life Sciences, Hebei University, Baoding City, Hebei Province, 071002, P.R. China.
  • 3 State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850, P.R. China. chenhongxia0626@163.com.
  • 4 Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, 421001, P.R. China. zhougq114@126.com.
  • 5 School of Life Sciences, Hebei University, Baoding City, Hebei Province, 071002, P.R. China. zhougq114@126.com.
  • 6 State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 100850, P.R. China. zhougq114@126.com.
  • 7 Collaborative Innovation Center for Personalized Cancer Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing City, Jiangsu Province, 211166, P.R. China. zhougq114@126.com.
PMID: 37640700 DOI: 10.1038/s41420-023-01619-3
Abstract

Human single-stranded DNA-binding protein homologs hSSB1 (SOSSB1) and hSSB2 (SOSSB2) make a vital impact on maintaining genome stability as the B subunits of the sensor of single-stranded DNA complex (SOSS). However, whether and how SOSSB1 and SOSSB2 modulate mutual expression is unclear. This study, demonstrated that the depletion of SOSSB1 in cells enhances the stability of the SOSSB2 protein, and conversely, SOSSB2 depletion enhances the stability of the SOSSB1 protein. The levels of SOSSB1 and SOSSB2 proteins are mutually regulated through their competitive binding with SOSSA which associates with the highly conservative OB-fold domain in SOSSB1 and SOSSB2. The destabilized SOSSB1 and SOSSB2 proteins can be degraded via the Proteasome pathway. Additionally, the simultaneous loss of SOSSB1 and SOSSB2 aggravates homologous recombination (HR)-mediated DNA repair defects, enhances cellular radiosensitivity and promotes cell Apoptosis. In conclusion, in this study, we showed that SOSSB1 and SOSSB2 positively regulate HR repair and the interaction between SOSSA and SOSSB1 or SOSSB2 prevents the degradation of SOSSB1 and SOSSB2 proteins via the Proteasome pathway.

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