Proteins encoded by the adenovirus E1A gene regulate both cellular and viral genes to mediate effects on cell cycle, differentiation, and cell growth control. We have identified the mouse mammary tumor virus (MMTV) promoter as a target of E1A action and investigated the role nucleoprotein structure plays in its response to E1A. Both 12 and 13 S forms target the MMTV promoter when it has a disorganized and accessible chromatin configuration. However, whereas the 13 S form is stimulatory, the 12 S form is repressive. When the MMTV promoter adopts an organized and repressed chromatin structure, it is targeted only by the 13 S form, which stimulates it. Although evidence indicates that E1A interacts with the SWI/SNF remodeling complex, E1A had no effect on chromatin remodeling at the MMTV promoter in organized chromatin. Analysis of E1A mutants showed that stimulation of the MMTV promoter is mediated solely through conserved region 3 and does not require interaction with Rb, p300/CBP-associated factor, or CBP/p300. Imaging analysis showed that E1A colocalizes with MMTV sequences in vivo, suggesting that it functions directly at the promoter. These results indicate that E1A stimulates the MMTV promoter in a fashion independent of chromatin conformation and through a direct mechanism involving interaction with the basal transcription machinery.
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http://dx.doi.org/10.1074/jbc.M200629200 | DOI Listing |
Proliferation and differentiation of the mammary gland during pregnancy is regulated by a wide variety of factors. Using gene expression data, we have predicted that the E2F5 transcription factor has a role in the mammary gland during pregnancy. Using CUT&RUN for E2F5 in combination with gene expression data revealed that there were a number of E2F5 target genes associated with gene expression in early pregnancy, suggesting a critical role.
View Article and Find Full Text PDFBasic Res Cardiol
August 2024
Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
Exercise is an effective way to alleviate breast cancer-induced cardiac injury to a certain extent. However, whether voluntary exercise (VE) activates cardiac signal transducer and activator of transcription 3 (STAT3) and the underlying mechanisms remain unclear. This study investigated the role of STAT3-microRNA(miRNA)-targeted protein axis in VE against breast cancer-induced cardiac injury.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
October 2024
Division of Nephrology-Hypertension, Department of Medicine, 0693, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093, USA; Center for Academic Research and Training in Anthropogeny (CARTA) University of California, La Jolla, San Diego, CA 92093, USA. Electronic address:
Due to alternative splicing in an ancestral DNA-binding domain (DBD) of the mineralocorticoid receptor (MR), humans contain two almost identical MR transcripts with either 984 amino acids (MR-984) or 988 amino acids (MR-988), in which their DBDs differ by only four amino acids, Lys,Cys,Ser,Trp (KCSW). Human MRs also contain mutations at two sites, codons 180 and 241, in the amino terminal domain (NTD). Together, there are five distinct full-length human MR genes in GenBank.
View Article and Find Full Text PDFBreast Cancer Res
May 2024
Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada.
Copy number gains in genes coding for Rho activating exchange factors as well as losses affecting genes coding for RhoGAP proteins are common in breast cancer (BC), suggesting that elevated Rho signaling may play an important role. Extra copies and overexpression of RHOC also occur, although a role for RhoC overexpression in driving tumor formation has not been assessed in vivo. To this end, we report on the development of a Rosa26 (R26)-targeted Cre-conditional RhoC overexpression mouse (R26).
View Article and Find Full Text PDFPLoS One
January 2024
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting in mammary tumor formation.
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