The functions of bHLH proteins

Abstract

Abstract Most known bHLH proteins are transcriptional regulators. That is, they are proteins that are able to alter the genetic programme of cells by repressing or activating specific genes, often genes involved in control of growth and differentiation. Not surprisingly, therefore, inappropriate expression of genes encoding both bHLH and bHLHZ proteins is frequently, associated with tumorigenesis and/or developmental dysfunctions. bHLH proteins can be divided into two broad functional groups by their patterns of expression. In the first group, expression is restricted to cells of a particular lineage. These are sometimes referred to as ‘class B’ bHLH proteins and examples are the myogenic factors MyoD, MyfS, MRF4 and myogenin. The second group (‘class A’ bHLH prqteins) are expressed fairly ubiquitously. These proteins, for example the E12 transcription factor, typically form heterodimers with the lineage-specific bHLH proteins. A similar classification holds for the bHLHZ proteins. One group comprises members whose expression is either tissue-specific (e.g. the restricted expression of N-Myc [524, 732, 733]) or else correlated with a specific cellular state, for example c-Myc in proliferation, apoptosis and, in some cell types, the potential to differentiate (reviewed in [3, 25, 31, 39, 47, 49]). In order to function, members of this first group must dimerize with members of the second group of bHLHZ proteins which are ubiquitously expressed (e.g. the obligate interaction between the Myc proteins and the ubiquitous bHLHZ protein Max (reviewed in [3])). The functions of both classes of bHLH and bHLHZ proteins are reviewed in this section.