NFX1-123: A potential therapeutic target in cervical cancer.

NFX1-123 is a splice variant isoform of the NFX1 gene. It is highly expressed in cervical cancers caused by HPV, and NFX1-123 is a protein partner with the HPV oncoprotein E6. Together, NFX1-123 and E6 affect cellular growth, longevity, and differentiation.

Post-Transcriptional Gene Regulation by HPV 16E6 and Its Host Protein Partners.

Human papillomavirus type 16 (HPV 16) is the most common oncogenic type of HPV in cervical, anogenital, and head and neck cancers, making HPV 16 an important high-risk HPV (HR HPV) type. To create an environment permissible for viral maintenance and growth and to initiate and support oncogenesis, the HR HPV protein E6 functions to dysregulate normal cellular processes. HR HPV type 16 E6 (16E6) has previously been shown to bind cellular proteins in order to transcriptionally activate genes and to target regulatory proteins for degradation.

The East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS.

The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women.

Cervical Cancer Development: Implications of HPV16 E6E7-NFX1-123 Regulated Genes.

High-risk human papillomavirus (HR HPV) causes nearly all cervical cancers, half of which are due to HPV type 16 (HPV16). HPV16 oncoprotein E6 (16E6) binds to NFX1-123, and dysregulates gene expression, but their clinical implications are unknown. Additionally, HPV16 E7's role has not been studied in concert with NFX1-123 and 16E6.

High expression of NFX1-123 in HPV positive head and neck squamous cell carcinomas.

Background: High-risk human papillomaviruses (HR HPV) cause nearly all cervical cancers and, in the United States, the majority of head and neck cancers (HNSCCs). NFX1-123 is overexpressed in cervical cancers, and NFX1-123 partners with the HR HPV type 16 E6 oncoprotein to affect multiple growth, differentiation, and immune response genes. However, neither the expression of NFX1-123 nor the levels of these genes have been investigated in HPV positive (HPV+) or negative (HPV-) HNSCCs.

NFX1, Its Isoforms and Roles in Biology, Disease and Cancer.

In 1989, two NFX1 protein products were identified as nuclear proteins with the ability to bind to X-box -elements. Since that publication, the gene and its homologs have been identified, from yeast to humans. This review article summarizes what is known about the gene across species.

Considerations for Child Cancer Survivors and Immunocompromised Children to Prevent Secondary HPV-associated Cancers.

Survivors of childhood cancer and other immunocompromised children are at high risk for the development of secondary human papillomavirus (HPV)-associated cancers. In this overview, the authors examine the epidemiology of vaccine efficacy, the natural history of HPV infections, and accelerated HPV-associated cancer development in these populations. The authors highlight the opportunities for preventive care and future research directives.

Genes Regulated by HPV 16 E6 and High Expression of NFX1-123 in Cervical Cancers.

Purpose: High-risk human papillomaviruses (HR HPV) cause cervical cancer, and in these cancers, HPV type 16 is the most common HR type. The HR viral oncogenes E6 and E7 partner with cellular proteins to drive cancer and modulate immune pathways; previously, we demonstrated in keratinocytes that HPV 16 E6 and high expression of the endogenous host protein partner NFX1-123 led to the increased expression of multiple genes, including Notch1, secretory leukocyte peptidase inhibitor (SLPI), and retinoic acid early transcript 1G (RAET1G). The present study was conducted to determine if NFX1-123 was highly expressed in cervical cancer and if genes increased by NFX1-123 and 16E6 in keratinocytes were also increased in cervical cancers.

HPV type 16 E6 and NFX1-123 augment JNK signaling to mediate keratinocyte differentiation and L1 expression.

The HPV life cycle is differentiation-dependent, with cellular differentiation driving initiation of the late, productive stage of the viral life cycle. Here, we identify a role for the protein NFX1-123 in regulating keratinocyte differentiation and events of the late HPV life cycle. NFX1-123 itself increased with differentiation of epithelial cells.

NFX1-123 is highly expressed in cervical cancer and increases growth and telomerase activity in HPV 16E6 expressing cells.

A significant contributor to women's cancer mortality worldwide is cervical cancer, which is caused by high-risk human papillomavirus (HR HPV). The two viral oncoproteins of HR HPV, E6 and E7, partner with host cell proteins to target oncogenic proteins and pathways. Previously, we have shown HR HPV type 16 E6 (16E6) interacts with the host protein NFX1-123 to target telomerase and cellular immortalization, requiring NFX1-123 to fully upregulate telomerase activity.

Human papillomavirus type 16 E6 and NFX1-123 mislocalize immune signaling proteins and downregulate immune gene expression in keratinocytes.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection, affecting an estimated 11% of the world's population. The high-risk HPV types (HR HPV) account for approximately 5% of the global burden of cancer and thus cause high morbidity and mortality. Although it is known that persistent infection with HR HPV is the greatest risk factor for developing HPV-associated cancer, and that the HPV early proteins E6 and E7 dysregulate immune detection by its host cells, the mechanisms of immune evasion by HR HPV are not well understood.

Telomerase Induction in HPV Infection and Oncogenesis.

Telomerase extends the repetitive DNA at the ends of linear chromosomes, and it is normally active in stem cells. When expressed in somatic diploid cells, it can lead to cellular immortalization. Human papillomaviruses (HPVs) are associated with and high-risk for cancer activate telomerase through the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT).

Activation of telomerase by HPVs.

Telomerase extends the ends of linear chromosomes, and its expression leads to cellular immortalization. In HPV-associated cancers, telomerase is universally detected, and this occurs by activation of the catalytic subunit of telomerase, hTERT. The expression of hTERT is affected by both high-risk HPV E6 and E7.

Human papillomavirus 16E6 and NFX1-123 potentiate Notch signaling and differentiation without activating cellular arrest.

High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1.

Skin and mucosal human papillomavirus seroprevalence in persons with Fanconi Anemia.

Persons with Fanconi anemia (FA) are at risk for human papillomavirus (HPV)-associated cancers; however, their natural HPV exposure and infection rates are unknown as is the adequacy with which they mount antibodies to HPV vaccination. This study aimed to determine, in 62 persons with FA, the seroprevalence of skin and mucosal HPV types, the seroprevalence in individuals self-reporting a history of HPV vaccination, and the factors associated with HPV seropositivity. A bead Luminex assay was used to determine seropositivity for HPV1, -2, and -4 (low-risk skin), -6 and -11 (low-risk mucosal, included in one HPV vaccine), -16 and -18 (high-risk mucosal, included in both HPV vaccines), and -52 and -58 (high-risk mucosal).

Detection of human papillomavirus in the oral cavities of persons with Fanconi anemia.

Objective: We conducted a cross-sectional study to describe the prevalence and correlates of type-specific human papillomavirus (HPV) DNA in the oral cavities of persons with Fanconi anemia.

Materials And Methods: Oral swabs were collected from 67 participants with Fanconi anemia and tested for 27 HPV genotypes using polymerase chain reaction-based methods.

Results: Participants were a mean of 18.

NFX1-123 and human papillomavirus 16E6 increase Notch expression in keratinocytes.

The high-risk human papillomavirus (HR HPV) E6 oncoprotein binds host cell proteins to dysregulate multiple regulatory pathways, including apoptosis and senescence. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and together they posttranscriptionally increase hTERT expression, the catalytic subunit of telomerase. NFX1-123 interacts with hTERT mRNA and stabilizes it, leading to greater telomerase activity and the avoidance of cellular senescence.

An unbiased in vivo screen reveals multiple transcription factors that control HPV E6-regulated hTERT in keratinocytes.

Activation of telomerase by human papillomavirus 16 (HPV16) E6 is a critical step for cell immortalization and transformation in human foreskin keratinocytes (HFKs). Multiple transcription factors have been identified as being involved in E6-induced hTERT expression. Here, we adapted an unbiased in vivo screen using a LacO-LacI system in human cells to discover hTERT promoter-interacting regulators.

Human papillomavirus vaccines: factors that affect vaccine knowledge and delivery.

Purpose: Although both vaccines are designed to prevent human papillomavirus (HPV) infection, HPV2 and HPV4 have different indications. This study sought to determine HPV and HPV vaccine knowledge among providers and examine factors affecting HPV vaccine delivery.

Methods: An e-mail survey was sent to adolescent health care providers via listserv.

Missed opportunities for adolescent vaccination, 2006-2011.

Objective: To describe missed opportunities for meningococcal (MCV); tetanus, diphtheria, acellular pertussis (Tdap); and human papillomavirus (HPV) vaccination among adolescents.

Methods: Retrospective electronic health record data review of adolescents aged 11-18 years at the time of their visit to a university-based pediatric practice in Seattle from 2006 to 2011. The primary outcome was missed vaccination opportunities, defined as the proportion of visits where a patient eligible for MCV, Tdap, and/or HPV remained unvaccinated.

Cytoplasmic poly(A) binding proteins regulate telomerase activity and cell growth in human papillomavirus type 16 E6-expressing keratinocytes.

The high-risk human papillomavirus (HPV) E6 and E7 oncoproteins are critical to the immortalization of keratinocytes. HPV type 16 (HPV16) E6 interacts with endogenous proteins to activate hTERT, the catalytic subunit of telomerase, thus avoiding cellular senescence signals. NFX1-123, the longer splice variant of NFX1, interacts with HPV16 E6, as well as cytoplasmic poly(A) binding proteins 1 and 4 (PABPC1 and PABPC4).