ABSTRACT Core Binding Factor (CBF) is required for the development of definitive hematopoiesis, and the CBF oncoproteins AML1-ETO, TEL-AML1, and CBFβ-SMMHC are commonly expressed in subsets

of acute leukemia. CBFβ-SMMHC slows the G1 to S cell cycle transition in hematopoietic cells, but the mechanism of this effect is uncertain. We have sought to determine whether inhibition of

CBF-mediated trans-activation is sufficient to slow proliferation. We demonstrate that activation of KRAB-AML1-ER, a protein containing the AML1 DNA-binding domain, the KRAB repression

domain, and the Estrogen receptor ligand binding domain, also slows G1, if its DNA-binding domain is intact. Also, exogenous AML1 overcame CBFβ-SMMHC-induced inhibition of proliferation.

bind p16INK4a, overcame cell cycle inhibition resulting from activation of KRAB-AML1-ER, although cdk4 did not accelerate proliferation when expressed alone. These findings indicate that

mutations which alter the expression of G1 regulatory proteins can overcome inhibition of proliferation by CBF oncoproteins. Access through your institution Buy or subscribe This is a

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ORDER AND COMMITMENT POINT IN CELLS PROLIFERATING WITHOUT CDK4/6 ACTIVITY Article Open access 20 October 2020 CDK19 REGULATES THE PROLIFERATION OF HEMATOPOIETIC STEM CELLS AND ACUTE MYELOID

LEUKEMIA CELLS BY SUPPRESSING P53-MEDIATED TRANSCRIPTION OF P21 Article 02 February 2022 NUCLEAR INTERACTING SET DOMAIN PROTEIN 1 INACTIVATION IMPAIRS GATA1-REGULATED ERYTHROID

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Yang Q, Goldstein AM, Tucker MA, Walker GJ, Hayward N and Dracopoli NC . 1996 _Nature Genet_ 12: 97–99 Download references ACKNOWLEDGEMENTS We thank W Wang and M Britos-Bray for technical

assistance, S Hiebert for the AML1B cDNA, C Sherr for the murine cdk4 and cyclin D2 cDNAs, and N Speck for CBFβ antisera. AD Friedman is supported by The Children's Cancer Foundation

and NIH grant HL51388 and is a Leukemia & Lymphoma Society Scholar. FJ Rauscher is a scholar of the Pew Program in Biomedical Sciences. F Bernardin is supported by the Foundation of

France Leukemia Committee and by the Leukemia Research Foundation. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Pediatric Oncology, The Johns Hopkins Oncology Center, Baltimore,

21231, Maryland, MD, USA Jianrong Lou, Wangsen Cao, Florence Bernardin & Alan D Friedman * The Wistar Institute, Philadelphia, 19104, Pennsylvania, PA, USA Kasirajan Ayyanathan & 

Frank J Rauscher III Authors * Jianrong Lou View author publications You can also search for this author inPubMed Google Scholar * Wangsen Cao View author publications You can also search

for this author inPubMed Google Scholar * Florence Bernardin View author publications You can also search for this author inPubMed Google Scholar * Kasirajan Ayyanathan View author

publications You can also search for this author inPubMed Google Scholar * Frank J Rauscher III View author publications You can also search for this author inPubMed Google Scholar * Alan D

Friedman View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lou, J.,

Cao, W., Bernardin, F. _et al._ Exogenous cdk4 overcomes reducedcdk4 RNA and inhibition of G1 progression in hematopoietic cells expressing a dominant-negative CBF – a model for overcoming

inhibition of proliferation by CBF oncoproteins. _Oncogene_ 19, 2695–2703 (2000). https://doi.org/10.1038/sj.onc.1203588 Download citation * Received: 04 November 1999 * Revised: 16 March

2000 * Accepted: 22 March 2000 * Published: 25 May 2000 * Issue Date: 18 May 2000 * DOI: https://doi.org/10.1038/sj.onc.1203588 SHARE THIS ARTICLE Anyone you share the following link with

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content-sharing initiative KEYWORDS * CBF * CBFβ-SMMHC * AML1-ETO * cdk4 * leukemia