ErbA: tumor suppressor turned oncogene?
Cancer has been commonly linked to aberrant proliferation and a failure of the transformed cells to differentiate. Activated proto-oncogenes are thought to provide continuous proliferation signals that enhance the growth of these cells. Conversely, cellular transformation may also be achieved by the inactivation of genes whose normal function is to constrain cell growth by either suppressing proliferation or inducing differentiation. Such an inactivation could result from dominant-negative mutations, leading to the expression of abnormal proteins that inhibit the function of their normal counterparts. A prototype example is the v-erbA oncogene of the avian erythroblastosis virus (AEV), which antagonizes the transcriptional regulatory function of the chicken c-ErbA/thyroid hormone receptors (c-ErbA/TR) and the structurally related retinoic acid receptors (RARs). The result of this inhibition is a loss of hormone responsiveness and hormone-induced differentiation. Here we have a parallel to the tumor suppressor gene where it is also a loss of function that induces the transformation process. In this way, the normal, hormone-activated c-ErbA/TRs and RARs act as growth suppressors because the resulting differentiated cells irreversibly lose proliferative potential. In this article, the properties of v-ErbA will be discussed in the context of c-ErbA/thyroid hormone and retinoic acid receptor function.
Damm
K
K
Department of Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany.
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D018774:Oncogene Proteins v-erbA; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000378:metabolism; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
D002352:Carrier Proteins; D018774:Oncogene Proteins v-erbA; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors