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Journal of Cell Science, Vol 113, Issue 22 3897-3905, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
JD Norton
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK. jnorton@essex.ac.uk
The ubiquitously expressed family of ID helix-loop-helix (HLH) proteins function as dominant negative regulators of basic HLH (bHLH) transcriptional regulators that drive cell lineage commitment and differentiation in metazoa. Recent data from cell line and in vivo studies have implicated the functions of ID proteins in other cellular processes besides negative regulation of cell differentiation. ID proteins play key roles in the regulation of lineage commitment, cell fate decisions and in the timing of differentiation during neurogenesis, lymphopoiesis and neovascularisation (angiogenesis). They are essential for embryogenesis and for cell cycle progression, and they function as positive regulators of cell proliferation. ID proteins also possess pro-apoptotic properties in a variety of cell types and function as cooperating or dominant oncoproteins in immortalisation of rodent and human cells and in tumour induction in Id-transgenic mice. In several human tumour types, the expression of ID proteins is deregulated, and loss- and gain-of-function studies implicate ID functions in the regulation of tumour growth, vascularisation, invasiveness and metastasis. More recent biochemical studies have also revealed an emerging 'molecular promiscuity' of mammalian ID proteins: they directly interact with and modulate the activities of several other families of transcriptional regulator, besides bHLH proteins.
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S. Fong, Y. Itahana, T. Sumida, J. Singh, J.-P. Coppe, Y. Liu, P. C. Richards, J. L. Bennington, N. M. Lee, R. J. Debs, et al. Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis PNAS, November 11, 2003; 100(23): 13543 - 13548. [Abstract] [Full Text] [PDF]
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