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PMID: 11073989 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle.

Molecular and cellular biology ·Vol. 20 ·No. 23 ·2000-12-00 ·Pages 8889-902

Miyake S, Sellers WR, Safran M, Li X, Zhao W, Grossman SR, Gan J, DeCaprio JA, Adams PD, Kaelin WG

Abstract

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

MeSH Terms
Acetyltransferases/antagonists & inhibitors Adenovirus E1A Proteins/metabolism Amino Acid Sequence CREB-Binding Protein Cell Cycle/physiology Cell Cycle Proteins Cell Differentiation Cloning, Molecular Down-Regulation Histone Acetyltransferases Molecular Sequence Data Nuclear Proteins/antagonists & inhibitors Protein Binding Protein Processing, Post-Translational Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-mdm2 Repressor Proteins Retinoblastoma Protein/metabolism Saccharomyces cerevisiae Proteins Trans-Activators/antagonists & inhibitors Transcriptional Activation Two-Hybrid System Techniques Ubiquitins/metabolism
Chemicals
Adenovirus E1A Proteins Cell Cycle Proteins EID1 protein, human Nuclear Proteins Proto-Oncogene Proteins Repressor Proteins Retinoblastoma Protein Saccharomyces cerevisiae Proteins Trans-Activators Ubiquitins Acetyltransferases CREB-Binding Protein Histone Acetyltransferases Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Miyake S
Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Sellers W R
Safran M
Li X
Zhao W
Grossman S R
Gan J
DeCaprio J A
Adams P D
Kaelin W G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.23.8889-8902.2000
Published
2000-12-00
Pages
8889-902
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86544
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.23.8889-8902.2000 PMC Full Text View journal details
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