Id family of helix-loop-helix proteins in cancer

• Published in: Nature reviews. Cancer Vol. 5; no. 8; pp. 603 - 614
• Main Authors: Perk, Jonathan, Iavarone, Antonio, Benezra, Robert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2005; Nature Publishing Group
• Subjects: Anaplasia - physiopathology; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cell Proliferation; DNA binding proteins; Genetic aspects; Helix-Loop-Helix Motifs - physiology; Humans; Inhibitor of Differentiation Protein 1; Models, Animal; Neoplasms - physiopathology; Neovascularization, Pathologic - physiopathology; Oncogenes; Physiological aspects; Repressor Proteins - physiology; review-article; Transcription Factors - physiology; United States
• DOI: 10.1038/nrc1673
• ISSN: 1474-175X

Key Points Inhibitor of DNA binding (Id) family members are key regulatory proteins in a wide range of developmental and cellular processes and function by inhibiting target proteins that include the basic helix-loop-helix transcription factors, members of the Ets protein family and retinoblastoma. Ids serve as downstream targets of known oncogenic pathways. However, the characterization of Id expression in human tumours and mouse models of cancer requires more careful analysis. Ids can contribute to tumorigenesis by inhibiting cell differentiation, stimulating proliferation and facilitating tumour neoangiogenesis. Id overexpression might mimic the activity of other oncogenes or the loss of tumour suppressor activity. The low postnatal expression of the Ids and their roles in tumorigenesis and tumour neoangiogenesis mark them as attractive targets for anti-cancer therapy. Over the past few decades, biologists have identified key molecular signatures associated with a wide range of human cancers. Recently, animal models have been particularly useful in establishing whether such signatures have functional relevance; the overexpression of pro-oncogenic or loss of anti-oncogenic factors have been evaluated for their effects on various tumour models. The aim of this review is to analyze the potential role of the inhibitor of DNA binding (Id) proteins in cancer and examine whether deregulated Id activity is tumorigenic and contributes to hallmarks of malignancy, such as loss of differentiation (anaplasia), unrestricted proliferation and neoangiogenesis.