Steroid regulation of terminal protein glycosyltransferase genes: molecular and functional homologies within sialyltransferase and fucosyltransferase families.

OBJECTIVE

Terminal glycosylations such as fucosylation and especially sialylation are crucial in maturation of proteins for their particular function. In cells and tissues where their function is under hormonal control, often terminal processes including glycosylations are tightly regulated by hormones. Therefore, it is not surprising that two key enzyme families involved in these steps, fucosyltransferases and sialyltransferases, are directly controlled by steroid hormones.

METHODS

Gene structure and protein sequences have been analyzed by set of Unix-based complex sequence analysis programs of the Wisconsin GCG package, and from some other resources. Protein secondary structure predictions were based on several independent programs and applications complementing each other depending on the algorithm used, all running on Unix platforms.

RESULTS

Comparison of these two types of enzymes from organisms where they are known to be under direct hormonal regulation has revealed that although sialyltransferases are broad family of proteins, the only known enzymes to be under hormonal control are alpha-2,6-sialyltransferases and in the case of fucosyl moieties transferring enzymes these are alpha-1,2/6-fucosyltransferases. Interestingly, hormonally regulated sialyltransferases from as evolutionary distant organisms as human and fruitfly share several important features including secondary structure characteristics encompassing sialyl L and S motifs in which they differ from other sialyltransferases. Analogous organizational and structural similarities were found also in hormonally regulated fucosyltransferases.

CONCLUSIONS

Data indicate that hormonal control of these classes of enzymes as a regulatory mechanism could be attained relatively early during the evolution in order to obtain selective control over specific protein modification process which plays an important role during ontogenic development.