title: Nuclear extracellular signal-regulated kinase 2 phosphorylates p53 at Thr55 in response to doxorubicin.
abstract: In this study, we showed that nuclear ERK2 phosphorylates p53 at Thr55 in response to doxorubicin. p53 was found to physically interact with ERK2 as evidenced by Western blotting of ERK2 coimmunoprecipitated complex. The gene fragment encoded for N-terminal 68 amino acids was subcloned and fused with 6-His. Each serine or threonine site in this fragment, the possible phosphorylation site, was mutated to alanine. The recombinant proteins were used as substrates in ERK2 kinase assay. The results show that ERK2 phosphorylated p53 at Thr55. Further, electromobility shift assay showed that the phosphorylation of p53 by nuclear ERK2 was closely related to the transactivating activity of p53. These findings suggest that ERK2 may play a role in response to DNA damage via interaction with p53.
authors: Cancer Research Center, College of Medicine, Taipei, Taiwan, Republic of China.
authors: P Y
authors: PY
authors: Yeh
authors: S E
authors: SE
authors: Chuang
authors: K H
authors: KH
authors: Yeh
authors: Y C
authors: YC
authors: Song
authors: A L
authors: AL
authors: Cheng
mesh_terms: D000409:Alanine; D019943:Amino Acid Substitution; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D003001:Cloning, Molecular; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000302:isolation & purification / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013912:Threonine; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms
chemical_list: D010750:Phosphoproteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D010769:Phosphothreonine; D013912:Threonine; D004317:Doxorubicin; D019950:Mitogen-Activated Protein Kinase 1; D000409:Alanine