The SUMO2/3 specific E3 ligase ZNF451-1 regulates PML stability

Koidl, S., Eisenhardt, N., Fatouros, C., Droescher, M., Chaugule, V. K. and Pichler, A. (2016) The SUMO2/3 specific E3 ligase ZNF451-1 regulates PML stability. International Journal of Biochemistry and Cell Biology, 79, pp. 478-487. (doi: 10.1016/j.biocel.2016.06.011) (PMID:27343429)

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Abstract

The small ubiquitin related modifier SUMO regulates protein functions to maintain cell homeostasis. SUMO attachment is executed by the hierarchical action of E1, E2 and E3 enzymes of which E3 ligases ensure substrate specificity. We recently identified the ZNF451 family as novel class of SUMO2/3 specific E3 ligases and characterized their function in SUMO chain formation. The founding member, ZNF451 isoform1 (ZNF451-1) partially resides in PML bodies, nuclear structures organized by the promyelocytic leukemia gene product PML. As PML and diverse PML components are well known SUMO substrates the question arises whether ZNF451-1 is involved in their sumoylation. Here, we show that ZNF451-1 indeed functions as SUMO2/3 specific E3 ligase for PML and selected PML components in vitro. Mutational analysis indicates that substrate sumoylation employs an identical biochemical mechanism as we described for SUMO chain formation. In vivo, ZNF451-1 RNAi depletion leads to PML stabilization and an increased number of PML bodies. By contrast, PML degradation upon arsenic trioxide treatment is not ZNF451-1 dependent. Our data suggest a regulatory role of ZNF451-1 in fine-tuning physiological PML levels in a RNF4 cooperative manner in the mouse neuroblastoma N2a cell-line.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chaugule, Dr Viduth
Authors: Koidl, S., Eisenhardt, N., Fatouros, C., Droescher, M., Chaugule, V. K., and Pichler, A.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:International Journal of Biochemistry and Cell Biology
Publisher:Elsevier
ISSN:1357-2725
ISSN (Online):1878-5875
Published Online:23 June 2016

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