A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators

Marie Vivian Wong, Sizun Jiang, Paaventhan Palasingam, Prasanna Kolatkar

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative group of helix-loop-helix (HLH) transcription regulators, are well-characterized key players in cellular fate determination during development in mammals as well as Drosophila. Although not oncogenes themselves, their upregulation by various oncogenic proteins (such as Ras, Myc) and their inhibitory effects on cell cycle proteins (such as pRb) hint at their possible roles in tumorigenesis. Furthermore, their potency as inhibitors of cellular differentiation, through their heterodimerization with subsequent inactivation of the ubiquitous E proteins, suggest possible novel roles in engineering induced pluripotent stem cells (iPSCs). We present the high-resolution 2.1Å crystal structure of ID2 (HLH domain), coupled with novel biochemical insights in the presence of a divalent ion, possibly calcium (Ca2+), in the loop of ID proteins, which appear to be crucial for the structure and activity of ID proteins. These new insights will pave the way for new rational drug designs, in addition to current synthetic peptide options, against this potent player in tumorigenesis as well as more efficient ways for stem cells reprogramming.

Original languageEnglish
Article numbere48591
JournalPLoS One
Volume7
Issue number10
DOIs
Publication statusPublished - 30 Oct 2012
Externally publishedYes

Fingerprint

Transcription
transcription factors
Ions
ions
Inhibitor of Differentiation Proteins
Carcinogenesis
Helix-Loop-Helix Motifs
Proteins
Stem cells
proteins
Induced Pluripotent Stem Cells
carcinogenesis
Cell Cycle Proteins
Drug Design
Oncogenes
Mammals
Drosophila
calcium
Up-Regulation
Stem Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators. / Wong, Marie Vivian; Jiang, Sizun; Palasingam, Paaventhan; Kolatkar, Prasanna.

In: PLoS One, Vol. 7, No. 10, e48591, 30.10.2012.

Research output: Contribution to journalArticle

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