biostudies-literatureLee SBU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSNational Research Foundation of Korea2089https://www.ebi.ac.uk/biostudies/studies/S-EPMC9018835biostudies-literatureUnknown13(1)Tissue-specific transcriptional activity is silenced in mitotic cells but it remains unclear whether the mitotic regulatory machinery interacts with tissue-specific transcriptional programs. We show that such cross-talk involves the controlled interaction between core subunits of the anaphase-promoting complex (APC) and the ID2 substrate. The N-terminus of ID2 is independently and structurally compatible with a pocket composed of core APC/C subunits that may optimally orient ID2 onto the APC^CDH1 complex. Phosphorylation of serine-5 by CDK1 prevented the association of ID2 with core APC, impaired ubiquitylation and stabilized ID2 protein at the mitosis-G1 transition leading to inhibition of basic Helix-Loop-Helix (bHLH)-mediated transcription. The serine-5 phospho-mimetic mutant Nature communicationsRegulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription.PMC9018835NRF-2020R1C1C1014281R01CA190891NRF-2021R1A5A8029876NRF-2020R1C1C1004015R01CA101644R01CA179044NRF-2021R1A5A2031612R01 CA239721R01 CA101644R01 CA179044R01CA131126R01 CA190891R01CA178546R01 CA178546U54CA193313R01 CA131126U54 CA193313Garofano LGan QCardozo TLasorella AKo AIavarone ASommer DKim KD'Angelo FLee SBFrangaj BfalseRegulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription.Tissue-specific transcriptional activity is silenced in mitotic cells but it remains unclear whether the mitotic regulatory machinery interacts with tissue-specific transcriptional programs. We show that such cross-talk involves the controlled interaction between core subunits of the anaphase-promoting complex (APC) and the ID2 substrate. The N-terminus of ID2 is independently and structurally compatible with a pocket composed of core APC/C subunits that may optimally orient ID2 onto the APC^CDH1 complex. Phosphorylation of serine-5 by CDK1 prevented the association of ID2 with core APC, impaired ubiquitylation and stabilized ID2 protein at the mitosis-G1 transition leading to inhibition of basic Helix-Loop-Helix (bHLH)-mediated transcription. The serine-5 phospho-mimetic mutant 2022-01-01T00:00:00Z2022 Apr2026-05-31T12:58:16.516Z2025-04-06T21:48:39.056ZS-EPMC90188353544062110.1038/s41467-022-29502-2