| First Author | Yu Y | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 3 | Pages | e57185 |
| PubMed ID | 23536762 | Mgi Jnum | J:199375 |
| Mgi Id | MGI:5502479 | Doi | 10.1371/journal.pone.0057185 |
| Citation | Yu Y, et al. (2013) GADD45alpha induction by nickel negatively regulates JNKs/p38 activation via promoting PP2Calpha expression. PLoS One 8(3):e57185 |
| abstractText | Growth arrest and DNA damage (GADD) 45alpha is a member of GADD inducible gene family, and is inducible in cell response to oxidative stress. GADD45alpha upregulation induces MKK4/JNK activation in some published experimental systems. However, we found here that the depletion of GADD45alpha (GADD45alpha-/-) in mouse embryonic fibroblasts (MEFs) resulted in an increase in the phosphorylation of MKK4/7, MKK3/6 and consequently specific up-regulated the activation of JNK/p38 and their downstream transcription factors, such as c-Jun and ATF2, in comparison to those in GADD45alpha+/+ MEFs cell following nickel exposure. This up-regulation of MKK-JNK/p38 pathway in GADD45alpha-/- cell could be rescued by the reconstitutional expression of HA-GADD45alpha in GADD45alpha-/- MEFs, GADD45alpha-/-(HA-GADD45alpha). Subsequent studies indicated that GADD45alpha deletion repressed expression of PP2Calpha, the phosphotase of MKK3/6 and MKK4/7, whereas ectopic expression of HA-PP2Calpha in GADD45alpha-/- cells attenuated activation of MKK3/6-p38 and MKK4/7-JNK pathways. Collectively, our results demonstrate a novel function and mechanism responsible for GADD45alpha regulation of MKK/MAPK pathway, further provides insight into understanding the big picture of GADD45alpha in the regulation of cellular responses to oxidative stress and environmental carcinogens. |
