PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Academic Article uri icon

abstract

  • IKKbeta serves as a central intermediate signaling molecule in the activation of the NF-kappaB pathway. However, the precise mechanism for the termination of IKKbeta activity is still not fully understood. Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, PPM1A and PPM1B, as IKKbeta phosphatases. Overexpression of PPM1A or PPM1B results in dephosphorylation of IKKbeta at Ser177 and Ser181 and termination of IKKbeta-induced NF-kappaB activation. PPM1A and PPM1B associate with the phosphorylated form of IKKbeta, and the interaction between PPM1A/PPM1B and IKKbeta is induced by TNFalpha in a transient fashion in the cells. Furthermore, knockdown of PPM1A and PPM1B expression enhances TNFalpha-induced IKKbeta phosphorylation, NF-kappaB nuclear translocation and NF-kappaB-dependent gene expression. These data suggest that PPM1A and PPM1B play an important role in the termination of TNFalpha-mediated NF-kappaB activation through dephosphorylating and inactivating IKKbeta.

published proceedings

  • Cell Signal

altmetric score

  • 6

author list (cited authors)

  • Sun, W., Yu, Y., Dotti, G., Shen, T., Tan, X., Savoldo, B., ... Yang, J.

citation count

  • 87

complete list of authors

  • Sun, Wenjing||Yu, Yang||Dotti, Gianpietro||Shen, Tao||Tan, Xiaojie||Savoldo, Barbara||Pass, Amy K||Chu, Meijin||Zhang, Dekai||Lu, Xiongbin||Fu, Songbin||Lin, Xia||Yang, Jianhua

publication date

  • January 2009