Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins.

Abstract	In mammalian cells, Id proteins coordinate proliferation and differentiation. Id2 is a dominant-negative antagonist of basic helix-loop-helix transcription factors and proteins of the retinoblastoma (Rb) family. Here we show that Id2-Rb double knockout embryos survive to term with minimal or no defects in neurogenesis and haematopoiesis, but they die at birth from severe reduction of muscle tissue. In neuroblastoma, an embryonal tumour derived from the neural crest, Id2 is overexpressed in cells carrying extra copies of the N-myc gene. In these cells, Id2 is in molar excess of the active form of Rb. The overexpression of Id2 results from transcriptional activation by oncoproteins of the Myc family. Cell-cycle progression induced by Myc oncoproteins requires inactivation of Rb by Id2. Thus, a dual connection links Id2 and Rb: during normal cell-cycle, Rb prohibits the action of Id2 on its natural targets, but oncogenic activation of the Myc-Id2 transcriptional pathway overrides the tumour-suppressor function of Rb.
Authors	A Lasorella, M Noseda, M Beyna, Y Yokota, A Iavarone
Journal	Nature (Nature) Vol. 407 Issue 6804 Pg. 592-8 (Oct 05 2000) ISSN: 0028-0836 [Print] England
PMID	11034201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	DNA-Binding Proteins ID2 protein, human Idb2 protein, mouse Inhibitor of Differentiation Protein 2 Proto-Oncogene Proteins c-myc Repressor Proteins Retinoblastoma Protein Transcription Factors
Topics	Animals Cell Cycle (physiology) Cell Line Crosses, Genetic DNA-Binding Proteins (genetics, metabolism) Embryo, Mammalian (metabolism) Embryonic and Fetal Development Female Gene Expression Regulation Hematopoiesis Humans Inhibitor of Differentiation Protein 2 Male Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Muscle, Skeletal (embryology, metabolism) Mutation Phosphorylation Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins c-myc (genetics, metabolism) Repressor Proteins Retinoblastoma (genetics, metabolism) Retinoblastoma Protein (genetics, metabolism) Signal Transduction Transcription Factors Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!