Document Detail


A non-covalent interaction between small ubiquitin-like modifier-1 and Zac1 regulates Zac1 cellular functions.
MedLine Citation:
PMID:  22227369     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Zac1, a zinc-finger protein that regulates apoptosis and cell cycle arrest 1, such as p53, can induce cell-cycle arrest and apoptosis. The transactivation and coactivation functions of Zac1 may occur at non-promyelocytic leukemia nuclear body (PML-NB) sites in the presence of other PML-NB components, including ubiquitin-conjugating 9 (Ubc9). It is unclear whether post-translational modification of Zac1 by the small ubiquitin-like modifier SUMO plays a role in the coactivation functions of Zac1 for the regulation of the p21 gene. Mutagenesis experiments revealed that the two SUMO-binding lysine residues of Zac1, K237 and K424, repress the transactivation activity of Zac1. Studies using a SUMO-1 C-terminal di-glycine motif mutant that is deficient in the ability to form covalent bonds with lysines, SUMO-1 (GA), and a dominant-negative Ubc9 construct (C93S) indicated that SUMO-1 might regulate Zac1 transactivation and coactivation via a non-covalent interaction. Unlike the wild-type Zac1, which induced apoptosis, the Zac1 (K237/424R) double mutant had the ability to induce autophagy. The functional role of p21 remains to be investigated. SUMO-1 selectively suppressed the induction of the p21 gene and protein by wild-type Zac1 but not by the Zac1 (K237/424R) double mutant. Moreover, wild-type Ubc9 but not Ubc9 (C93S) further potentiated the suppression of SUMO-1 in all Zac1-induced p21 promoter activities. Our data reveal that p21 may be an important factor for the prevention of Zac1-induced apoptosis without affecting autophagosome formation. This work indicates that Zac1 functions are regulated, at least in part, via non-covalent interactions with SUMO-1 for the induction of p21, which is important for the modulation of apoptosis.
Authors:
Shu-Ting Liu; Yung-Lung Chang; Wei-Ming Wang; Min-Huey Chung; Wei-Shiang Lin; Wei-Yuan Chou; Shih-Ming Huang
Related Documents :
12804199 - Biochemical and functional aspects of gonadotrophin-releasing hormone and gonadotrophins.
21994179 - New insights into the role of stat3 in ibd.
7953699 - Interleukin-2 stimulates the secretion of arginine vasopressin but not corticotropin-re...
21772279 - Return to homeostasis: downregulation of nf-κb responses.
67339 - Depressed lymphocyte function after bereavement.
7721259 - Pituitary-thyroid axis and immune system: a reciprocal neuroendocrine-immune interaction.
7540689 - The nitric oxide synthase inhibitor, l-ng-monomethylarginine, reduces carrageenan-induc...
23114889 - Immune heterogeneity in neuroinflammation: dendritic cells in the brain.
10373279 - Differential immune system changes with acute and persistent stress for optimists vs pe...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-27
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  -     ISSN:  1878-5875     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, ROC.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Controlled systemic delivery by polymeric implants enhances tissue and plasma curcumin levels compar...
Next Document:  Characterization of a myostatin gene (MSTN1) from spotted halibut (Verasper variegatus) and associat...