A naturally occurring variant of HPV-16 E7 exerts increased transforming activity through acquisition of an additional phospho-acceptor site.

  title={A naturally occurring variant of HPV-16 E7 exerts increased transforming activity through acquisition of an additional phospho-acceptor site.},
  author={Amira Zine El Abidine and Vjekoslav Tomaić and Rahima Bel Haj Rhouma and Paola Massimi and Ikram Guizani and Samir Boubaker and Emna Ennaifer and Lawrence Banks},

The Role of HPV E7 in Maintenance of Cell Transformation

HPV E7 continue to play an important role in maintenance of transformed phenotype and targeting E7 phosphorylation could be a potential therapeutic strategy in HPV-induced malignancy.

The HPV-18 E7 CKII phospho acceptor site is required for maintaining the transformed phenotype of cervical tumour-derived cells

Genetic editing of the HPV-18 E7 CKII recognition site in C4-1 cervical tumour-derived cells is performed, and it is found that phosphorylation of E7 plays a direct role in the ability of E6 to activate AKT signaling, which in turn is required for optimal levels of MMP secretion.

Human papillomavirus oncoproteins and post-translational modifications: generating multifunctional hubs for overriding cellular homeostasis

The direct consequences of some of the most common PTMs of E6 and E7 are discussed, and how this impacts upon the multi-functionality of these viral proteins, and thereby contribute to the viral life cycle and to the induction of malignancy.

Proteasomal degradation of p130 facilitate cell cycle deregulation and impairment of cellular differentiation in high-risk Human Papillomavirus 16 and 18 E7 transfected cells.

The findings provide strong evidence that the localisation of nuclear p130 nuclear was disrupted by HPV16/18 E7 led to the deregulation of the cell cycle and the impairment of cellular differentiation ultimately lead to cellular transformation.

Modeling and Molecular Dynamics of the 3D Structure of the HPV16 E7 Protein and Its Variants

It is concluded that the mutations induced by the variants in N29S and H51N have a significant influence on the 3D structure of the E7 protein of HPV16, which could be related to the oncogenic capacity of this protein.

Metabolic Reprogramming in Cancer: Role of HPV 16 Variants

The role of HPV 16 E6 and E7 variants in metabolic reprogramming and their contribution to developing and preserving the malignant phenotype of cancers associated with HPV 16 infection are discussed.

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

The natural history of HPV infection and the transforming properties of various HPV genera will be described, with a particular focus on describing the state of knowledge about the role of cutaneous HPV types in NMSC.

E6/E7 Variants of Human Papillomavirus 16 Associated with Cervical Carcinoma in Women in Southern Mexico

Results highlight the importance of analyzing the combinations of E6/E7 variants in HPV 16 infection and suggest that AA-a*E6-C732/C789/G795, AA-c*E7-C 732/ C789/ G795, and A176/G350*E 7-p can be useful markers for predicting CC development.

Protein kinase CK2 – diverse roles in cancer cell biology and therapeutic promise

Aspects of CK2 cellular roles and targeting in cancer are discussed in the present review, with focus on nuclear and mitochondrial functions and prostate, breast and head and neck malignancies.



Systematic Analysis of the Amino Acid Residues of Human Papillomavirus Type 16 E7 Conserved Region 3 Involved in Dimerization and Transformation

It is indicated that E7 does not need to exist as a stable dimer in order to transform cells and also several novel E7 mutants that abrogate transformation are identified.

Differential phosphorylation of the HPV-16 E7 oncoprotein during the cell cycle.

The human papillomavirus type 16 encodes two principal oncoproteins, E6 and E7. The E7 protein has been shown to deregulate the cell cycle through interactions with a variety of proteins involved in

The E7 protein of human papillomavirus type 16 is phosphorylated by casein kinase II.

It is concluded that E7 is phosphorylated in vivo only at serines within the predicted CKII site and that CKII, or a CKII-like enzyme, participates in the reaction.

Human Papillomavirus Type 16 E6 Amino Acid 83 Variants Enhance E6-Mediated MAPK Signaling and Differentially Regulate Tumorigenesis by Notch Signaling and Oncogenic Ras

A novel link between the E6 oncoprotein and activation of mitogen-activated protein kinase (MAPK) signaling is established and it is found that activated MAPK signaling cooperates with deregulated Notch1 signaling to recreate features of HPV-driven invasive cervical carcinomas.

Degradation of the Retinoblastoma Tumor Suppressor by the Human Papillomavirus Type 16 E7 Oncoprotein Is Important for Functional Inactivation and Is Separable from Proteasomal Degradation of E7

Using the SAOS2 flat-cell assay as a biological indicator for pRB function, it is demonstrated that pRB degradation, not solely binding, is important for the E7-induced inactivation of pRB.

Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis.

It is demonstrated that the ability of E7 to induce destabilization of pRB and stabilization of p53 coincides with E7-mediated transformation and apoptosis, and the domains of E 7 that are required for predisposing cells to undergo apoptosis in response to growth arrest signals.

Targeting mechanism of the retinoblastoma tumor suppressor by a prototypical viral oncoprotein

A mechanistic model of the interaction of the Rb protein with a viral target in solution is discussed, integrated with structural data and the analysis of other cellular and viral proteins, which provided information about the balance of interactions involving the R b protein and how these determine the progression into either the normal cell cycle or transformation.

Three Regions of the pRB Pocket Domain Affect Its Inactivation by Human Papillomavirus E7 Proteins

It is shown here that the efficient inactivation of pRB in HeLa cells does not simply depend on the integrity of the LXCXE-binding cleft, and that multiple site-directed mutants that alter conserved surfaces of the pRB pocket domain cause He La cells to accumulate in G1.

Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53

The purification of E6-AP and the cloning of its corresponding cDNA, which contains a novel open reading frame encoding 865 amino acids, is reported, suggesting a model by which E6 deregulates cell growth control by the elimination of the p53 tumor suppressor protein.

E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway.

Evidence is provided for HPV-16 E7-induced enhanced degradation of Rb protein via a ubiquitin-proteasome pathway and a second mechanism of oncogenic transformation by E7 is suggested, in addition to its previously identified ability to sequester Rb from E2F.