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Summary
Heme is essential for protein synthesis in red blood cells. Without heme, a protein kinase is activated, inhibiting globin synthesis by blocking initiation factors.
Area of Science:
- Molecular Biology
- Biochemistry
- Cellular Regulation
Background:
- Globin synthesis in reticulocyte lysates requires heme.
- Heme absence activates an inhibitor of polypeptide chain initiation.
Purpose of the Study:
- To elucidate the mechanism of heme's regulation of globin synthesis.
- To identify the molecular players involved in inhibiting protein synthesis.
Main Methods:
- Investigated the role of protein kinases in heme-regulated translation.
- Analyzed the phosphorylation of eukaryotic initiation factor 2 (eIF-2) and its impact on protein synthesis.
Main Results:
- Identified a cyclic AMP-independent protein kinase that phosphorylates eIF-2.
- Phosphorylation of eIF-2 by this kinase inhibits its interaction with eIF-2-stimulating protein (ESP).
- Heme inhibits a cyclic AMP-dependent protein kinase, preventing the activation of the eIF-2 kinase inhibitor.
Conclusions:
- Heme regulates globin synthesis by inhibiting a protein kinase cascade.
- This regulatory mechanism prevents the phosphorylation of eIF-2, thereby ensuring efficient protein initiation.