Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1

10Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

Abstract

MEKK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates the MAPK JNK and is required for microtubule inhibitor-induced apoptosis in B cells. Here, we find that apoptosis induced by actin disruption via cytochalasin D and by the protein phosphatase 1/2A inhibitor okadaic acid also requires MEKK1 activation. To elucidate the functional requirements for activation of the MEKK1-dependent apoptotic pathway, we created mutations within MEKK1. MEKK1-deficient cells were complemented with MEKK1 containing mutations in either the ubiquitin interacting motif (UIM), plant homeodomain (PHD), caspase cleavage site or the kinase domain at near endogenous levels of expression and tested for their sensitivity to each drug. We found that both the kinase activity and the PHD domain of MEKK1 are required for JNK activation and efficient induction of apoptosis by drugs causing cytoskeletal disruption. Furthermore, we discovered that modification of MEKK1 and its localization depends on the integrity of the PHD.

Cite

CITATION STYLE

APA

Tricker, E., Arvand, A., Kwan, R., Chen, G. Y., Gallagher, E., & Cheng, G. (2011). Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1. PLoS ONE, 6(2). https://doi.org/10.1371/journal.pone.0017310

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free