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- Title
Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription.
- Authors
Lee, Sang Bae; Garofano, Luciano; Ko, Aram; D'Angelo, Fulvio; Frangaj, Brulinda; Sommer, Danika; Gan, Qiwen; Kim, KyeongJin; Cardozo, Timothy; Iavarone, Antonio; Lasorella, Anna
- Abstract
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 APCCDH1 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 of ID2 that inefficiently bound core APC remained stable during mitosis, delayed exit from mitosis and reloading of bHLH transcription factors on chromatin. It also locked cells into a "mitotic stem cell" transcriptional state resembling the pluripotent program of embryonic stem cells. The substrates of APCCDH1 SKP2 and Cyclin B1 share with ID2 the phosphorylation-dependent, D-box-independent interaction with core APC. These results reveal a new layer of control of the mechanism by which substrates are recognized by APC. Tissue-specific transcriptional activity is silenced in mitotic cells. Here the authors reveal a general phosphorylation-dependent mechanism of recognition for the anaphase-promoting complex (APC) substrates, and show that the APC targets ID2 during the establishment of post-mitotic transcription.
- Subjects
EMBRYONIC stem cells; MITOSIS; TRANSCRIPTION factors; TRANSGENIC organisms; ANTIGEN presenting cells; UBIQUITINATION; STEM cells
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-29502-2