Protein intrinsic disorder and human papillomaviruses

Increased amount of disorder in E6 and E7 oncoproteins from high risk HPVs

Vladimir N. Uversky, Ann Roman, Christopher J. Oldfield, A. Dunker

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

It is recognized now that many functional proteins or their long segments are devoid of stable secondary and/or tertiary structure and exist instead as very dynamic ensembles of conformations. They are known by different names including natively unfolded, intrinsically disordered, intrinsically unstructured, rheomorphic, pliable, and different combinations thereof. Many important functions and activities have been associated with these intrinsically disordered proteins (IDPs), including molecular recognition, signaling, and regulation. It is also believed that disorder of these proteins allows function to be readily modified through phosphorylation, acetylation, ubiquitination, hydroxylation, and proteolysis. Bioinformatics analysis revealed that IDPs comprise a large fraction of different proteomes. Furthermore, it is established that the intrinsic disorder is relatively abundant among cancer-related and other disease-related proteins and IDPs play a number of key roles in oncogenesis. There are more than 100 different types of human papillomaviruses (HPVs), which are the causative agents of benign papillomas/warts, and cofactors in the development of carcinomas of the genital tract, head and neck, and epidermis. With respect to their association with cancer, HPVs are grouped into two classes, known as low (e.g., HPV-6and HPV-11) and high-risk (e.g., HPV-16 and HPV-18) types. The entire proteome of HPV includes sixnonstructural proteins [E1, E2, E4, E5, E6, and E7 (the latter two are known to function as oncoproteins in the high-risk HPVs)] and two structural proteins (L1 and L2). To understand whether intrinsic disorder plays a role in the oncogenic potential of different HPV types, we have performed a detailed bioinformatics analysis of proteomes of high-risk and low-risk HPVs with the major focus on E6 and E7 oncoproteins. The results of this analysis are consistent with the conclusion that high-risk HPVs are characterized by the increased amount of intrinsic disorder in transforming proteins E6 and E7.

Original languageEnglish
Pages (from-to)1829-1842
Number of pages14
JournalJournal of Proteome Research
Volume5
Issue number8
DOIs
StatePublished - Aug 2006

Fingerprint

Oncogene Proteins
Intrinsically Disordered Proteins
Proteome
Bioinformatics
Proteins
Proteolysis
Acetylation
Computational Biology
Molecular recognition
Hydroxylation
Phosphorylation
Conformations
Human papillomavirus 11
Human papillomavirus 18
Warts
Human papillomavirus 16
Association reactions
Ubiquitination
Papilloma
Epidermis

Keywords

  • Cancer
  • HPV
  • Intrinsic protein disorder
  • Oncoprotein
  • Papillomavirus
  • Transforming protein

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Protein intrinsic disorder and human papillomaviruses : Increased amount of disorder in E6 and E7 oncoproteins from high risk HPVs. / Uversky, Vladimir N.; Roman, Ann; Oldfield, Christopher J.; Dunker, A.

In: Journal of Proteome Research, Vol. 5, No. 8, 08.2006, p. 1829-1842.

Research output: Contribution to journalArticle

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