title: High risk HPV E6 oncoproteins impair the subcellular distribution of the four and a half LIM-only protein 2 (FHL2).
abstract: HPVs are the causative agents of approximately 5% of all human cancers, with cervical cancer being the most predominant. To understand the mechanism of action of the viral E6 oncoprotein, we analysed the effects of E6 upon potential cellular target proteins. One candidate is FHL-2, involved in the regulation of signal transduction pathways from the multimeric complexes assembled at focal adhesions. We show that both HPV E6 and E6(⁎) can interact with FHL-2 in vitro, but unlike most E6 targets, FHL-2 does not appear to be an E6 degradation target. Analysis of the patterns of FHL-2 distribution within HPV-positive tumour-derived cells shows a significant alteration in the pattern of FHL-2 localisation when compared to non-HPV containing cells. This perturbation of FHL-2 distribution is proteasome-dependent and inhibition of E6 expression restores the normal distribution of FHL-2. These results confirm FHL-2 as a new interacting partner of the HPV-E6 oncoproteins.
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, México.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Manzo-Merino
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Massimi
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste, Italy. Electronic address: banks@icgeb.org.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080, México. Electronic address: lizanosoberon@gmail.com.
authors.forename: Marcela
authors.initials: M
authors.lastname: Lizano
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C105987:FHL2 protein, human; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D014157:Transcription Factors
keywords: FHL-2; HPV-E6 oncoprotein; Proteasome