Dataset Information

The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.

ABSTRACT: Expression of viral proteins causes important epigenetic changes leading to abnormal cell growth. Whether viral proteins directly target histone methyltransferases (HMTs), a key family enzyme for epigenetic regulation, and modulate their enzymatic activities remains elusive. Here we show that the E6 proteins of both low-risk and high-risk human papillomavirus (HPV) interact with three coactivator HMTs, CARM1, PRMT1 and SET7, and downregulate their enzymatic activities in vitro and in HPV-transformed HeLa cells. Furthermore, these three HMTs are required for E6 to attenuate p53 transactivation function. Mechanistically, E6 hampers CARM1- and PRMT1-catalyzed histone methylation at p53-responsive promoters, and suppresses the binding of p53 to chromatinized DNA independently of E6-mediated p53 degradation. p53 pre-methylated at lysine-372 (p53K372 mono-methylation) by SET7 protects p53 from E6-induced degradation. Consistently, E6 downregulates p53K372 mono-methylation and thus reduces p53 protein stability. As a result of the E6-mediated inhibition of HMT activity, expression of p53 downstream genes is suppressed. Together, our results not only reveal a clever approach for the virus to interfere with p53 function, but also demonstrate the modulation of HMT activity as a novel mechanism of epigenetic regulation by a viral oncoprotein.

SUBMITTER: Hsu CH

PROVIDER: S-EPMC3349118 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.

Hsu C-H CH Peng K-L KL Jhang H-C HC Lin C-H CH Wu S-Y SY Chiang C-M CM Lee S-C SC Yu W C Y WC Juan L-J LJ

Oncogene 20111003 18

Expression of viral proteins causes important epigenetic changes leading to abnormal cell growth. Whether viral proteins directly target histone methyltransferases (HMTs), a key family enzyme for epigenetic regulation, and modulate their enzymatic activities remains elusive. Here we show that the E6 proteins of both low-risk and high-risk human papillomavirus (HPV) interact with three coactivator HMTs, CARM1, PRMT1 and SET7, and downregulate their enzymatic activities in vitro and in HPV-transfo ...[more]

PMID: 21963854

Similar Datasets

Project description:Cervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6™ Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (<CIN2) and histological positive group (CIN2, CIN3 and invasive carcinoma). Overall, HPV16/18-E6 oncoprotein was detected in 30.6% of cervical samples, 20.3% of self-collected vaginal samples and 21% of urine samples. Regarding the clinical sensitivity, the HPV16/18-E6 oncoprotein was not detected in CIN2 cases, and was detected at low rates in CIN3 cases. The clinical sensitivity of the HPV16/18-E6 oncoprotein for detecting invasive cervical cancer was 70% for cervical scrapes, 55% for self-collected vaginal samples and 52% for urine samples. This study reports the urinary detection of E6 oncoprotein in vivo for the first time and our results suggest that this detection is only for invasive/microinvasive lesions. Then, further protocol development and standardization to achieve a clinical sensitivity for CIN2/3 detection close to what can be achieved for invasive lesions using the physician collected cervical is needed.

Dataset Information

The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.

Publications

The HPV E6 oncoprotein targets histone methyltransferases for modulating specific gene transcription.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets