Cells Degrade a Novel Inhibitor of Differentiation with E1A-Like Properties upon Exiting the Cell Cycle

• DOI: 10.1128/mcb.20.23.8889-8902.2000
• Publication Date: 2002-07-27T10:03:53Z
• Authors: Satoshi Miyake; William R. Sellers; Michal Safran; Xiaotong Li; Wenqing Zhao; Steven R. Grossman; Jianmin Gan; James A. DeCaprio; Peter D. Adams; William G. Kaelin
• Keywords: Retinoblastoma protein; F-box protein

Control of proliferation and differentiation by the retinoblastoma tumor suppressor protein (pRB) related family members depends upon their interactions with key cellular substrates. Efforts to identify such targets led isolation a novel protein, EID-1 (for E1A-like inhibitor 1). Here, we show that is potent link this activity its ability inhibit p300 (and highly molecule, CREB-binding or CBP) histone acetylation activity. rapidly degraded proteasome as cells exit cell cycle. Ubiquitination requires an intact C-terminal region also necessary for stable binding pRB, two proteins bind ubiquitin ligase MDM2. A pRB variant can EID1, but not MDM2, stabilizes in cells. Thus, may act at nodal point couples cycle transcriptional activation genes required differentiation.