PMID- 16775354
OWN - NLM
STAT- MEDLINE
DCOM- 20060810
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 80
IP  - 13
DP  - 2006 Jul
TI  - Human papillomavirus E7 oncoprotein dysregulates steroid receptor coactivator 1 
      localization and function.
PG  - 6669-77
AB  - High-risk human papillomaviruses (HPVs) are present in virtually all cervical 
      carcinomas. However, the majority of women infected with high-risk HPVs do not 
      develop cervical cancer. Therefore, cofactors must contribute to the development 
      and progression of cervical cancer. Although numerous studies have implicated 
      steroid hormones as cofactors in the initiation and progression of cervical 
      neoplasia, the molecular mechanisms by which they contribute to cervical 
      carcinogenesis are currently unknown. These observations led us to investigate a 
      newly discovered association of the high-risk HPV type 16 (HPV16) E7 oncoprotein 
      with steroid receptor coactivator 1 (SRC-1), an essential component of steroid 
      hormone signaling. HPV16 E7 has been previously reported to interact with p300 
      and p300/CBP-associated factor (PCAF), members of some SRC-1 transcriptional 
      complexes. We demonstrate here that HPV16 E7 associates in vivo and in vitro with 
      SRC-1 independently of p300 and PCAF. Luciferase reporter constructs under the 
      control of either the interleukin-8 promoter or a promoter containing 
      multimerized synthetic estrogen response elements were used to determine the 
      effect of high- and low-risk HPV E7 expression on SRC-1-mediated transcription. 
      In addition, histone acetyltransferase (HAT) assays were performed to determine 
      the effect of HPV E7 on SRC-1-associated HAT activity. These experiments reveal 
      that HPV16 E7 expression down-regulates SRC-1-mediated transcription and 
      SRC-1-associated HAT activity. SRC-1 localization experiments show that SRC-1 is 
      relocalized to the cytoplasm in the presence of high- and low-risk HPV E7 
      proteins. Our data suggest that HPV E7 proteins dysregulate hormone-dependent 
      gene expression by association with and relocalization of SRC-1. Dysregulation of 
      SRC-1 localization and function by HPV E7 may provide insight into the molecular 
      mechanisms by which steroid hormones act as cofactors in the induction and 
      progression of cervical neoplasia.
FAU - Baldwin, Amy
AU  - Baldwin A
AD  - The Channing Laboratory, Brigham and Women's Hospital and Department of Medicine, 
      Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA.
FAU - Huh, Kyung-Won
AU  - Huh KW
FAU - Munger, Karl
AU  - Munger K
LA  - eng
GR  - F32 CA112978/CA/NCI NIH HHS/United States
GR  - T32 CA 09031-28/CA/NCI NIH HHS/United States
GR  - R01 CA 66980/CA/NCI NIH HHS/United States
GR  - F32 CA 112978-01A1/CA/NCI NIH HHS/United States
GR  - R01 CA066980/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 2.3.1.48 (p300-CBP-associated factor)
SB  - IM
MH  - Carcinoma/enzymology/virology
MH  - Cell Cycle Proteins/*metabolism
MH  - *Cell Transformation, Viral
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Gonadal Steroid Hormones/metabolism
MH  - HeLa Cells
MH  - Histone Acetyltransferases/*metabolism
MH  - Humans
MH  - Nuclear Receptor Coactivator 1
MH  - Oncogene Proteins, Viral/*metabolism
MH  - Papillomavirus E7 Proteins
MH  - Protein Binding
MH  - Protein Transport
MH  - *Signal Transduction
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - Uterine Cervical Neoplasms/enzymology/virology
MH  - p300-CBP Transcription Factors/metabolism
PMC - PMC1488981
EDAT- 2006/06/16 09:00
MHDA- 2006/08/11 09:00
PMCR- 2006/11/01
CRDT- 2006/06/16 09:00
PHST- 2006/06/16 09:00 [pubmed]
PHST- 2006/08/11 09:00 [medline]
PHST- 2006/06/16 09:00 [entrez]
PHST- 2006/11/01 00:00 [pmc-release]
AID - 80/13/6669 [pii]
AID - 2497-05 [pii]
AID - 10.1128/JVI.02497-05 [doi]
PST - ppublish
SO  - J Virol. 2006 Jul;80(13):6669-77. doi: 10.1128/JVI.02497-05.