Many studies have detected dysregulated expression of CK2 in human cancers ( 46). With hundreds of putative substrates identified through in vitro studies ( 27), CK2 has been linked to fundamental cellular processes including the regulation of DNA transcription and damage responses ( 13, 14), protein translation and stability ( 5, 42), and circadian rhythms ( 22). Thus, CK2α appears to play an essential and uncompensated role in mammalian development.ĬK2 is a ubiquitous and highly conserved serine/threonine kinase. Defects in the formation of the heart lead to hydrops fetalis and are likely the cause of embryonic lethality. CK2α −/− embryos die in mid-gestation, with abnormalities including open neural tubes and reductions in the branchial arches. Embryos lacking CK2α have a marked reduction in CK2 activity in spite of the presence of the CK2α′ subunit. We have used homologous recombination to disrupt the CK2α gene in the mouse germ line. Gene-targeting experiments have demonstrated that in mice, the CK2β gene is required for early embryonic development, while the CK2α′ subunit appears to be essential only for normal spermatogenesis. CK2 has many substrates in cells, and key roles in yeast cell physiology have been uncovered by introducing subunit mutations. Protein kinase CK2 (formerly casein kinase II) is a highly conserved and ubiquitous serine/threonine kinase that is composed of two catalytic subunits (CK2α and/or CK2α′) and two CK2β regulatory subunits.
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