Sumoylation-dependent control of homotypic and heterotypic synergy by the Krüppel-type zinc finger protein ZBP-89

Sergey Chupreta, Holly Brevig, Longchuan Bai, Juanita L. Merchant, Jorge A. Iñiguez-Lluhí

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The Krüppel-like transcription factor ZBP-89 is a sequence-specific regulator that plays key roles in cellular growth and differentiation especially in endodermal and germ cell lineages. ZBP-89 shares with other members of the Sp-like family an overlapping sequence specificity for GC-rich sequences in the regulatory regions of multiple genes. Defining the mechanisms that govern the intrinsic function of ZBP-89 as well as its competitive and non-competitive functional interactions with other regulators is central to understand how ZBP-89 exerts its biological functions. We now describe that post-translational modification of ZBP-89 by multiple small ubiquitin-like modifier (SUMO) isoforms occurs at two conserved synergy control motifs flanking the DNA binding domain. Functionally sumoylation did not directly alter the ability of ZBP-89 to compete with other Sp-like factors from individual sites. At promoters bearing multiple response elements, however, this modification inhibited the functional cooperation between ZBP-89 and Sp1. Analysis of the properties of ZBP-89 in cellular contexts devoid of competing factors indicated that although on its own it behaves as a modest activator it potently synergizes with heterologous activators such as the glucocorticoid receptor. Notably we found that when conjugated to ZBP-89, SUMO exerts a strong inhibitory effect on such synergistic interactions through a critical conserved functional surface. By regulating higher order functional interactions, sumoylation provides a reversible post-translational mechanism to control the activity of ZBP-89.

Original languageEnglish (US)
Pages (from-to)36155-36166
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number50
DOIs
StatePublished - Dec 14 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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