Abstract
Nemo-like kinase (NLK), a proline-directed serine/threonine kinase regulated by phosphorylation, can be localized in the cytosol or in the nucleus. Whether the localization of NLK can affect cell survival or cell apoptosis is yet to be disclosed. In the present study we found that NLK was mainly localized in the nuclei of breast cancer cells, in contrast to a cytosolic localization in non-cancerous breast epithelial cells. The nuclear localization of NLK was mediated through direct interaction with Heat shock protein 27 (HSP27) which further protected cancer cells from apoptosis. The present study provides evidence of a novel mechanism by which HSP27 recognizes NLK in the breast cancer cells and prevents NLK-mediated cell apoptosis.
Highlights
MAP kinases are classified into conventional or atypical enzymes, based on their phosphorylation status and activation by MAP kinase kinase (MAPKK) family members
Endogenous Nemo-like kinase (NLK) is localized to the nuclei of breast cancer cells
To test the hypothesis that Heat shock protein 27 (HSP27) is responsible for sustained nuclear localization of NLK, we reduced the level of HSP27 in cancer cells, by using two different siRNA oligos (Figure 5A), and investigated NLK localization
Summary
MAP kinases are classified into conventional or atypical enzymes, based on their phosphorylation status and activation by MAP kinase kinase (MAPKK) family members. Homeodomain-interacting protein kinase (HIPK2) [2,3,4,5], MAPKKK TGF-b-activated kinase 1 (TAK1) [2,6,7], and p38 MAPK [8], are enzymes that have been suggested to activate NLK through phosphorylation. NLK can phosphorylate several proteins essential for the regulation of different signaling pathways, such as Wnt/b-catenin [6,7,9,10], Notch [11,12], and Smad [13]. NLK has been shown to negatively regulate Wnt/b-catenin signaling by phosphorylation of the complex LEF1/TCFs, which facilitates ubiquitination and degradation of this complex [7]. SETDB1 (SET domain bifurcated 1), a histone methyltransferase, is phosphorylated by NLK, upon
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
