Repression of Cyclin D1 - a Novel Function of Myc

Philipp, A., Schneider, A., Vasrik, I., Finke, K., Xiong, Y., Beach, D., Alitalo, K., Eilers, M. (June 1994) Repression of Cyclin D1 - a Novel Function of Myc. Molecular and Cellular Biology, 14 (6). pp. 4032-4043. ISSN 0270-7306

URL: http://www.ncbi.nlm.nih.gov/pubmed/8196642
DOI: 10.1128/MCB.14.6.4032

Abstract

Constitutive expression of human MYC represses mRNA levels of cyclin D1 in proliferating BALB/c-3T3 fibroblasts. We expressed a series of mutant alleles of MYC and found that downregulation of cyclin D1 is distinct from previously described properties of MYC. In particular, we found that association with Max is not required for repression of cyclin D1 by MYC in vivo. Conversely, the integrity of a small amino-terminal region (amino acids 92 to 106) of MYC is critical for repression of cyclin D1 but dispensable for transformation of established RAT1A cells. Runoff transcription assays showed that repression occurs at the level of transcription initiation. We cloned the promoter of the gene for human cyclin D1 and found that it lacks a canonical TATA element. Transcription starts at an initiator element similar to that of the adenovirus major late promoter; this element can be directly bound by USF in vitro. Expression of MYC represses the cyclin D1 promoter via core promoter elements and antagonizes USF-mediated transactivation. Taken together, our data define a new pathway for gene regulation by MYC and show that the cyclin D1 gene is a target gene for repression by MYC.

Item Type: Paper
Uncontrolled Keywords: HUMAN C-MYC MYELOCYTOMATOSIS VIRUS MC29 HUMAN HEMATOPOIETIC-CELLS DNA-BINDING RETINOBLASTOMA PROTEIN ACTIVATES TRANSCRIPTION GENE-EXPRESSION N-MYC ORNITHINE DECARBOXYLASE DIFFERENTIAL EXPRESSION
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Matt Covey
Date: June 1994
Date Deposited: 01 May 2015 19:07
Last Modified: 01 May 2015 19:07
PMCID: PMC358769
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31468

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