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Molecular and Cellular Biology, February 2003, p. 831-841, Vol. 23, No. 3
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.3.831-841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Identification of Homeodomain Proteins, PBX1 and PREP1, Involved in the Transcription of Murine Leukemia Virus

Sheng-Hao Chao, John R. Walker, Sumit K. Chanda, Nathanael S. Gray, and Jeremy S. Caldwell*

Genomics Institute of the Novartis Research Foundation, San Diego, California 92121

Received 24 June 2002/ Returned for modification 1 August 2002/ Accepted 10 October 2002

Cyclin-dependent kinase inhibitors (CDKIs) have been shown to block human immunodeficiency virus and herpes simplex virus. It is hypothesized that CDKIs block viral replication by inhibiting transcription of specific cellular genes. Here we find that three CDKIs, flavopiridol, purvalanol A, and methoxy-roscovitine, block Moloney murine leukemia virus (MLV) transcription events. Using gene expression microarray technology to examine the inhibitory effects of CDKIs, we observed a cellular gene, the pre-B-cell leukemia transcription factor 1 (Pbx1) gene, down-regulated by CDKI treatment. The PBX consensus element (PCE), TGATTGAC, is conserved in the long terminal repeats of several murine retroviruses, including Moloney MLV. Mutations in the PCE completely inhibited viral transcription whereas overexpression of PBX1 and a PBX1-associated protein, PREP1, enhanced viral transcription. The interaction between the PCE and PBX1-PREP1 proteins was confirmed by gel shift experiments. Blocking PBX1 protein synthesis resulted in a significant decrease in viral transcription. Collectively, our results represent the first work demonstrating that the homeodomain proteins PBX1 and PREP1 are cellular factors involved in Moloney MLV transcription regulation.


* Corresponding author. Mailing address: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121. Phone: (858) 812-1511. Fax: (858) 812-1920. E-mail: jcaldwell{at}gnf.org.


Molecular and Cellular Biology, February 2003, p. 831-841, Vol. 23, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.3.831-841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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