A non-covalent interaction between small ubiquitin-like modifier-1 and Zac1 regulates Zac1 cellular functions

Shu Ting Liu, Yung Lung Chang, Wei Ming Wang, Min Huey Chung, Wei Shiang Lin, Wei Yuan Chou, Shih Ming Huang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Ubiquitin
Apoptosis
Transcriptional Activation
Cell Cycle Checkpoints
Lysine
Leukemia
Cells
Mutagenesis
Covalent bonds
Zinc Fingers
Autophagy
Post Translational Protein Processing
Glycine
Zinc
Proteins
Genes
Modulation
Experiments

Keywords

  • Coactivation
  • SUMO-1
  • SUMO-interacting motif
  • SUMOylation
  • Zac1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

A non-covalent interaction between small ubiquitin-like modifier-1 and Zac1 regulates Zac1 cellular functions. / Liu, Shu Ting; Chang, Yung Lung; Wang, Wei Ming; Chung, Min Huey; Lin, Wei Shiang; Chou, Wei Yuan; Huang, Shih Ming.

In: International Journal of Biochemistry and Cell Biology, Vol. 44, No. 3, 03.2012, p. 547-555.

Research output: Contribution to journalArticle

Liu, Shu Ting ; Chang, Yung Lung ; Wang, Wei Ming ; Chung, Min Huey ; Lin, Wei Shiang ; Chou, Wei Yuan ; Huang, Shih Ming. / A non-covalent interaction between small ubiquitin-like modifier-1 and Zac1 regulates Zac1 cellular functions. In: International Journal of Biochemistry and Cell Biology. 2012 ; Vol. 44, No. 3. pp. 547-555.
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