Nuclear extracellular signal-regulated kinase 2 phosphorylates p53 at Thr55 in response to doxorubicin

Yeh, PY Chuang, SE Yeh, KH Song, YC Cheng, AL

Py. Yeh et al., Nuclear extracellular signal-regulated kinase 2 phosphorylates p53 at Thr55 in response to doxorubicin, BIOC BIOP R, 284(4), 2001, pp. 880-886

31

INGLESE

Article

Biochemistry & Biophysics

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

0006-291X → ACNP

284

4

2001

880 - 886

ISI

0006-291X(20010622)284:4<880:NESK2P>2.0.ZU;2-M

In this study, we showed that nuclear ERK2 phosphorylates p53 at Thr55 in r esponse to doxorubicin. p53 was found to physically interact with ERK2 as e videnced by Western blotting of ERK2 coimmunoprecipitated complex. The gene fragment encoded for N-terminal 68 amino acids was subcloned and fused wit h 6-His. Each serine or threonine site in this fragment, the possible phosy phorylation site, was mutated to alanine. The recombinant proteins were use d as substrates in ERK2 kinase assay. The results show that ERK2 phosphoryl ated p53 at Thr55. Further, electromobility shift assay showed that the pho sphorylation of p53 by nuclear ERK2 was closely related to the transactivat ing activity of p53. These findings suggest that ERK2 may play a role in re sponse to DNA damage via interaction with p53. (C) 2001 Academic Press.