PgmNr D1076: Modulation of CRL4^Cdt2 activity in the syncytial embryo.

Authors:
J. Speciale ¹ ; B. Duronio ² ; C. Swanson ¹

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Institutes
1) Arcadia University, Glenside, PA; 2) University of North Carolina, Chapel Hill,.

Keyword: developmental modulation

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Abstract:

CRL4^Cdt2-mediated protein destruction is a developmentally critical phenomenon required for proper progression of both canonical and non-canonical cell cycles. CRL4^Cdt2 induces replication-coupled destruction of its substrates, which include the Drosophila proteins Double-parked (Dup), E2f1, and Dacapo (Dap).  Despite its critical role in overseeing S phase progression and maintaining genome stability, we have observed modulation of CRL4^Cdt2 function in several developmental contexts.  For example, our preliminary data suggest that CRL4^Cdt2 activity may be modified in the rapid, non-canonical cell cycles of the syncytial embryo.  More specifically, we have observed differential stability of substrates in this context: Dup appears to be targeted for destruction during S phase as normal, while E2f1 and Dap are stable.  These data suggest that CRL4^Cdt2 is active, but that at least two of its substrates are protected during these early cell cycles.  We have identified sequences within the E2f1 protein that are required for protection in the early embryo.  Continuing experiments seek to elucidate the mechanism, and ultimately the developmental function, of differential CRL4^Cdt2 substrate stabilization during early embryonic development. Our findings suggest that CRL4^Cdt2 activity may be modulated to accommodate unique cell cycle programs such as the rapid cycles of the syncytial embryo.