Related Experiment Video
Updated: Aug 7, 2026
09:20
In situ Subcellular Fractionation of Adherent and Non-adherent Mammalian Cells
Published on: July 23, 2010
Human papillomavirus E7 oncoprotein dysregulates steroid receptor coactivator 1 localization and function
Amy Baldwin1, Kyung-Won Huh, Karl Münger
1The Channing Laboratory, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA.
Journal of Virology
|June 16, 2006
Summary
High-risk human papillomaviruses (HPVs) contribute to cervical cancer, but cofactors are key. This study reveals HPV16 E7 oncoprotein disrupts steroid hormone signaling by interacting with SRC-1, impacting gene expression and cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- High-risk human papillomaviruses (HPVs) are linked to cervical cancer, yet not all infections lead to cancer, suggesting cofactor involvement.
- Steroid hormones are implicated as cofactors in cervical neoplasia, but their precise molecular mechanisms remain unclear.
Purpose of the Study:
- To investigate the molecular interaction between the high-risk HPV16 E7 oncoprotein and steroid receptor coactivator 1 (SRC-1).
- To determine the functional consequences of this interaction on SRC-1-mediated transcription and its associated histone acetyltransferase (HAT) activity.
Main Methods:
- In vivo and in vitro association assays to confirm HPV16 E7 and SRC-1 interaction.
- Luciferase reporter assays to assess SRC-1-mediated transcription.
- Histone acetyltransferase (HAT) assays to evaluate SRC-1's enzymatic activity.
- Cellular localization studies to track SRC-1 in the presence of HPV E7 proteins.
Main Results:
- HPV16 E7 associates with SRC-1 independently of p300 and PCAF.
- HPV16 E7 down-regulates SRC-1-mediated transcription and SRC-1-associated HAT activity.
- High- and low-risk HPV E7 proteins cause SRC-1 relocalization to the cytoplasm.
Conclusions:
- HPV E7 proteins disrupt hormone-dependent gene expression through physical association with and cytoplasmic relocalization of SRC-1.
- Dysregulation of SRC-1 by HPV E7 offers insight into how steroid hormones act as cofactors in cervical neoplasia development and progression.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
01:03Rous Sarcoma Virus (RSV) and Cancer
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...