MyD genes in negative growth control.

Two interrelated cellular processes are invoked simultaneously upon induction of differentiation, the regulated progression of cells through successive stages of cell differentiation and growth inhibition which ultimately leads to growth arrest. In tissues with rapid cell turnover terminally differentiated cells undergo programmed cell death. Terminal differentiation, thus, represents one form of negative growth control. It was surmised that the molecular engine which drives the differentiation process forward requires induction of positive regulators of terminal cell differentiation, to be found among differentiation primary response genes, as well as suppression of negative regulators, which correspond to genes which control cellular growth. This line of thought has prompted the isolation of myeloid differentiation primary response (MyD) genes activated in the absence of de novo protein synthesis, upon IL-6 induced terminal differentiation of murine M1 myeloblastic leukemia cells, where the cells growth arrest and ultimately undergo programmed cell death. As delineated in this review many of the genes identified as MyD genes, including both known genes [IRF-1, (AP-1)Fos/Jun.EGR-1] and novel ones (MyD88, MyD116, MyD118), turned out to play a role in negative growth control, including growth suppression and apoptosis, in many cell types, of both hematopoietic and non hematopoietic origins.