| Literature DB >> 25959309 |
Julia Sajman1, Drora Zenvirth1, Mor Nitzan2, Hanah Margalit3, Kobi J Simpson-Lavy1, Yuval Reiss4, Itamar Cohen5, Tommer Ravid5, Michael Brandeis1.
Abstract
Ndd1 activates the Mcm1-Fkh2 transcription factor to transcribe mitotic regulators. The anaphase-promoting complex/cyclosome activated by Cdh1 (APC/C(Cdh1)) mediates the degradation of proteins throughout G1. Here we show that the APC/C(Cdh1) ubiquitinates Ndd1 and mediates its degradation, and that APC/C(Cdh1) activity suppresses accumulation of Ndd1 targets. We confirm putative Ndd1 targets and identify novel ones, many of them APC/C(Cdh1) substrates. The APC/C(Cdh1) thus regulates these proteins in a dual manner—both pretranscriptionally and post-translationally, forming a multi-layered feedforward loop (FFL). We predict by mathematical modelling and verify experimentally that this FFL introduces a lag between APC/C(Cdh1) inactivation at the end of G1 and accumulation of genes transcribed by Ndd1 in G2. This regulation generates two classes of APC/C(Cdh1) substrates, early ones that accumulate in S and late ones that accumulate in G2. Our results show how the dual state APC/C(Cdh1) activity is converted into multiple outputs by interactions between its substrates.Entities:
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Year: 2015 PMID： 25959309 DOI： 10.1038/ncomms8075
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919