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For whom the cells toll |
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![]() In a recent paper in Developmental Cell (2002, 2, 159170), Andreas Bergman and colleagues at the Howard Hughes Medical Institute in Cambridge, MA, and the Weizmann Institute of Science in Rehovot, Israel, examined trophic survival signaling in midline glia cells of Drosophila (glia cells are important in the proper development of the nervous system). The trophic theory is based on the premise that cellular intrinsic suicide is the default position unless the cell is signaled by secreted factors from neighboring cells to survive. Although this theory has been validated by many studies, Bergman and co-workers are the first to elucidate the step-by-step pathway by which the survival signals mediate the suppression of the apoptotic cellular program. In the glia cells, Bergman and colleagues discovered through analysis of mutants that a growth factor known as SPITZ activated the pathway known as RAS/MAPK, which had already been shown to promote growth and suppress apoptosis in various cancers. The researchers showed that the pathway functioned by inhibiting the activity of the HID protein, which thereby enabled glia cell survival. (HID is produced by the hid genethe convention being that the gene is listed in lower-case italics, the protein for that gene in uppercase nonitalics.) For example, mutational activation of MAPK promotes the survival of extra glia cells; the absence of MAPK promotes cell death; and the overexpression of the hid gene induces apoptosis. The researchers further discovered that MAPK suppresses hid activity in two ways: down-regulation of hid transcription, and phosphorylation of the HID produced. Although other pathways undoubtedly have profound effects on regulating apoptosis, this research is important because it describes the complete mechanism of a single pathway. MARK S. LESNEY |
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