Transferrin receptor 1(TfR1),a widely expressed type Ⅱ transmembrane glycoprotein located on the plasma membrane,is well known for its established role in cellular iron uptake.Nevertheless,emerging evidence implies t...Transferrin receptor 1(TfR1),a widely expressed type Ⅱ transmembrane glycoprotein located on the plasma membrane,is well known for its established role in cellular iron uptake.Nevertheless,emerging evidence implies that TfR1 exhibits previously unrecognized noncanonical functions.Herein,we demonstrated the nuclear translocation of TfR1 and revealed the interaction between TfR1 and p53 within the nucleus.Through comprehensive analyses at the proteomic,genomic,and transcriptomic levels,we demonstrated that this interaction significantly influences the transcriptional activity of p53 on its downstream target genes,which are highly enriched in DNA damage repair functions.Specifically,our investigation revealed the indispensable role of nuclear TfR1 in the regulation of the nucleotide excision repair(NER)pathway,exemplified by the transcriptional regulation of XPC.展开更多
基金financially supported by the National Key Research and Development Program of China(2021YFA1201102)the National Natural Science Foundation of China(No.32301163,82072054)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y2023024)the Beijing Nova Program(Z211100002121023,20220484207).
文摘Transferrin receptor 1(TfR1),a widely expressed type Ⅱ transmembrane glycoprotein located on the plasma membrane,is well known for its established role in cellular iron uptake.Nevertheless,emerging evidence implies that TfR1 exhibits previously unrecognized noncanonical functions.Herein,we demonstrated the nuclear translocation of TfR1 and revealed the interaction between TfR1 and p53 within the nucleus.Through comprehensive analyses at the proteomic,genomic,and transcriptomic levels,we demonstrated that this interaction significantly influences the transcriptional activity of p53 on its downstream target genes,which are highly enriched in DNA damage repair functions.Specifically,our investigation revealed the indispensable role of nuclear TfR1 in the regulation of the nucleotide excision repair(NER)pathway,exemplified by the transcriptional regulation of XPC.
