Small Ubiquitin-like Modifier (SUMO) Modification of Zinc Finger Protein 131 Potentiates Its Negative Effect on Estrogen Signaling

Abstract

Background: A poorly characterized zinc finger protein, ZNF131, is implicated as a negative regulator of estrogen receptor ␣ target gene expression. Results: ZNF131 is a target of covalent SUMOylation via hPc2, which potentiates its inhibitory effect on estrogen signaling. Conclusion: Estrogen signaling is down-regulated through the SUMOylation of ZNF131. Significance: Covalent SUMO1 modification of ZNF131 negatively regulates estrogen receptor-mediated signaling and estrogen-induced cell proliferation in breast cancer cells.

UHRF2, a Ubiquitin E3 Ligase, Acts as a Small Ubiquitin-like Modifier E3 Ligase for Zinc Finger Protein 131

“…In addition, pretreatment with the proteasomal inhibitor MG-132 enhanced ZNF131 ubiquitination ( Fig. 2A), supporting data from our previous report (30). However, UHRF2 did Immunoprecipitates were immunoblotted with the indicated antibodies as indicated.…”

“…As described previously (30), overexpression of the SUMO protein generated di-and tri-SUMOylated forms of ZNF131 in HEK293 cells (2xS, 3xS), which likely occurs because of increased SUMO levels and subsequent excessive SUMOylation. Nevertheless, ZNF131 is mono-SUMOylated at the lysine 567 residue in physiological conditions using either endogenous SUMO1 or SUMO2/3 (30). Similarly, although multiple SUMOylated UHRF2 bands were generated in cells overexpressing SUMO protein (Fig.…”

“…NM_003352) and its conjugationdefective mutant (pRK5-V5-SUMO1-GG and pRK5-V5-SU-MO1-AA), and Myc-tagged hPc2 (GenBank TM accession no. NM_003655; pRK5-Myc-hPc2), were constructed as described previously (30). The plasmid encoding 3xMyc-tagged human UBC9 (3ϫMyc-UBC9) was a kind gift from Dr. Y. K. Jang (Yonsei University, Seoul, Korea).…”

“…After screening a human fetal brain cDNA library, we isolated several binding partners of ZNF131, including hPc2, a previously reported SUMO E3 ligase of ZNF131 (30), and UHRF2 (data not shown). Because UHRF2 has ubiquitin E3 ligase activity, we examined the relationship between these two proteins.…”

BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells

“…Kaiso can interact with DNA through a specific binding sequence, as well as a methylated cytosine of DNA. Znf131 interacts with E3 ubiquitin ligases, CBX4 and UHRF2, for its SUMOylation (14,15). The function of Znf131 in the development of various tissues including T lineage has not been explored yet.…”