Identification of a developmental timer regulating the stability of embryonic cyclin A and a new somatic A-type cyclin at gastrulation.
We have identified a second Xenopus cyclin A, called cyclin A2. Cyclin A2 is a 46.6-kD protein that shows a greater homology to human cyclin A than to the previously identified Xenopus cyclin A1. It is present throughout embryonic development (up to stage 46 at least) and is found in adult tissues as well as in Xenopus tissue culture cell lines. In contrast, cyclin A1 is present in eggs and early embryos but cannot be detected in late embryos or in tissue culture cells. We have found that the maternally stored pools of mRNAs encoding both of these cyclin A proteins are stable until the onset of gastrulation and then are degraded abruptly. At this time, new transcription replaces cyclin A2 mRNA. Interestingly, we have also observed a dramatic change in the stability of the cyclin A proteins at this time. Prior to the onset of gastrulation, cyclin A1 protein is stable during interphase of the cell cycle. At gastrulation, however, both A1 and A2 proteins turn over rapidly during interphase of the cell cycle. Together, these results indicate that developmental programs controlling cyclin A protein and mRNA stability are activated at gastrulation. We have shown that this program is independent of new transcription beginning at the mid-blastula transition. Furthermore, treatment of early stage embryos with cycloheximide demonstrates that activation of this degradative program is independent of cell division and translation. Collectively, our observations suggest that a previously uncharacterized timing mechanism activates new degradative pathways at the onset of gastrulation, which could play an essential role in releasing cells from maternal programming.
Howe
J A
JA
Department of Biology, University of California at San Diego, La Jolla 92093-0347, USA.
Howell
M
M
Hunt
T
T
Newport
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D003001:Cloning, Molecular; D019925:Cyclin A; D056751:Cyclin A2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005775:Gastrula / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis / Q000196:embryology*
C503725:CCNA2 protein, Xenopus; C503721:CCNA2 protein, human; D019925:Cyclin A; D056751:Cyclin A2; D016213:Cyclins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018844:Cyclin-Dependent Kinases