Mahogunin-mediated α-tubulin ubiquitination via noncanonical K6 linkage regulates microtubule stability and mitotic spindle orientation

49Citations
Citations of this article
55Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Mahogunin ring finger-1 (MGRN1) is a cytosolic ubiquitin ligase whose disruption or interaction with some isoforms of cytosolically exposed prion protein leads to spongiform neurodegeneration and also lack of which results in reduced embryonic viability due to mispatterning of the left-right (LR) axis during development. Here we demonstrate an interaction between the cytoskeletal protein α-tubulin and MGRN1. In cultured cell systems, loss of the ubiquitin E3 ligase activity of MGRN1 results in spindle misorientation and decreased α-tubulin polymerization, an effect also seen in primary cells. α-Tubulin was post-translationally modified by MGRN1 via noncanonical K6-linked polyubiquitination. This was significant because expression of catalytically inactive MGRN1 and/or ubiquitin mutant capable of only monoubiquitination resulted in similar mitotic spindle misorientation. The modulatory effect of MGRN1 was specific for α-tubulin and similar changes could not be detected in β- or γ-tubulin. However, catalytic inactivation of MGRN1 did not abrogate monoubiquitination of α-tubulin, thus unraveling a unique dual mode of ubiquitination by an unknown E3 ligase and MGRN1. MGRN1-mediated α-tubulin modification, and hence its stability, may highlight a key event in the LR patterning during embryogenesis. © 2014 Macmillan Publishers Limited.

Cite

CITATION STYLE

APA

Srivastava, D., & Chakrabarti, O. (2014). Mahogunin-mediated α-tubulin ubiquitination via noncanonical K6 linkage regulates microtubule stability and mitotic spindle orientation. Cell Death and Disease, 5(2). https://doi.org/10.1038/cddis.2014.1

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