Identification of a novel LXXLL motif in α-actinin 4-spliced isoform that is critical for its interaction with estrogen receptor α and co-activators

Simran Khurana, Sharmistha Chakraborty, Xuan Zhao, Yu Liu, Dongyin Guan, Minh Lam, Wei Huang, Sichun Yang, Hung Ying Kao

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

α-Actinins (ACTNs) are a family of proteins cross-linking actin filaments that maintain cytoskeletal organization and cell motility. Recently, it has also become clear that ACTN4 can function in the nucleus. In this report, we found that ACTN4 (full length) and its spliced isoform ACTN4 (Iso) possess an unusual LXXLL nuclear receptor interacting motif. Both ACTN4 (full length) and ACTN4 (Iso) potentiate basal transcription activity and directly interact with estrogen receptor α, although ACTN4 (Iso) binds ERα more strongly. We have also found that both ACTN4 (full length) and ACTN4 (Iso) interact with the ligand-independent and the ligand-dependent activation domains of estrogen receptor α. Although ACTN4 (Iso) interacts efficiently with transcriptional co-activators such as p300/CBP-associated factor (PCAF) and steroid receptor co-activator 1 (SRC-1), the full length ACTN4 protein either does not or does so weakly. More importantly, the flanking sequences of the LXXLL motif are important not only for interacting with nuclear receptors but also for the association with co-activators. Taken together, we have identified a novel extended LXXLL motif that is critical for interactions with both receptors and co-activators. This motif functions more efficiently in a spliced isoform of ACTN4 than it does in the full-length protein.

Original languageEnglish
Pages (from-to)35418-35429
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number42
DOIs
Publication statusPublished - 2012 Oct 12

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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