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

Autor: Amira Zine El Abidine, Ikram Guizani, Samir Boubaker, Paola Massimi, Vjekoslav Tomaić, Lawrence Banks, Emna Ennaifer, Rahima Bel Haj Rhouma
Přispěvatelé: Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée aux Maladies Infectieuses (LR11IPT04), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Rudjer Boskovic Institute [Zagreb], Tumour Virology Laboratory [Trieste], International Centre for Genetic Engineering and Biotechnology (ICGEB), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), This work was supported in part by a research grant to LB from the Associazione Italiana per la Ricerca sul Cancro. Amira Zine El Abidine is a recipient of an ICGEB Arturo Falaschi Pre-doctoral Fellowship and was supported by the Ministry of Higher Education and Scientific Research of Tunisia (LR111PT04)., We are grateful to Miranda Thomas for valuable comments on the manuscript.
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Papillomavirus E7 Proteins
Amino Acid Motifs
MESH: Papillomavirus E7 Proteins/metabolism
Retinoblastoma Protein
MESH: Human papillomavirus 16/physiology
MESH: Amino Acid Motifs
Phosphorylation
TBP
E7
Human papillomavirus 16
MESH: Papillomavirus E7 Proteins/chemistry
HPV
CKII phosphorylation
pRb
MESH: Human papillomavirus 16/genetics
3. Good health
Cell biology
MESH: TATA-Box Binding Protein/genetics
Biochemistry
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Amino acid change
Cancer development
Protein Binding
MESH: Retinoblastoma Protein/metabolism
MESH: TATA-Box Binding Protein/metabolism
MESH: Papillomavirus Infections/metabolism
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
MESH: Retinoblastoma Protein/genetics
MESH: Cell Transformation
Viral
03 medical and health sciences
Virology
Humans
MESH: Protein Binding
MESH: Human papillomavirus 16/chemistry
Human papillomavirus
Binding Sites
MESH: Humans
MESH: Phosphorylation
TATA-Box Binding Protein
Papillomavirus Infections
MESH: Papillomavirus Infections/virology
Cell Transformation
Viral
030104 developmental biology
MESH: Binding Sites
MESH: Papillomavirus Infections/genetics
MESH: Papillomavirus E7 Proteins/genetics
Function (biology)
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Virology
Virology, Elsevier, 2017, 500, pp.218-225. ⟨10.1016/j.virol.2016.10.023⟩
ISSN: 0042-6822
1096-0341
DOI: 10.1016/j.virol.2016.10.023⟩
Popis: International audience; Human Papillomavirus E6 and E7 play critical roles in cancer development, although not all isolates of the viral oncoproteins are identical. A common E7 variant encodes an amino acid change at N29S. We show that this change increases the levels of phosphorylation by CKII by creating an additional phospho-acceptor site at S29. This confers increased phospho-dependent interaction with a number of cellular targets, including TATA Box Binding Protein (TBP) and pRb. A further consequence is an increased ability to target pRb and p130 for degradation. Biologically, these biochemical differences are reflected in an increased ability of the N29S variant to transform primary rodent cells. This is the first study to demonstrate an important biochemical change in E7 function caused by a naturally occurring variation, and we suggest that the N29S variant merits further assessment to determine whether it has an increased association with the development of HPV-associated malignancies.
Databáze: OpenAIRE
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