New Insights into Protein Hydroxylation and Its Important Role in Human Diseases

Giada Zurlo, Jianping Guo, Mamoru Takada, Wenyi Wei, Qing Zhang

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Protein hydroxylation is a post-translational modification catalyzed by 2-oxoglutarate-dependent dioxygenases. The hydroxylation modification can take place on various amino acids, including but not limited to proline, lysine, asparagine, aspartate and histidine. A classical example of this modification is hypoxia inducible factor alpha (HIF-α) prolyl hydroxylation, which affects HIF-α protein stability via the Von-Hippel Lindau (VHL) tumor suppressor pathway, a Cullin 2-based E3 ligase adaptor protein frequently mutated in kidney cancer. In addition to protein stability regulation, protein hydroxylation may influence other post-translational modifications or the kinase activity of the modified protein (such as Akt and DYRK1A/B). In other cases, protein hydroxylation may alter protein-protein interaction and its downstream signaling events in vivo (such as OTUB1, MAPK6 and eEF2K). In this review, we highlight the recently identified protein hydroxylation targets and their pathophysiological roles, especially in cancer settings. Better understanding of protein hydroxylation will help identify novel therapeutic targets and their regulation mechanisms to foster development of more effective treatment strategies for various human cancers.

Original languageEnglish (US)
Pages (from-to)208-220
Number of pages13
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1866
Issue number2
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Fingerprint

Hydroxylation
Proteins
Protein Stability
Post Translational Protein Processing
Cullin Proteins
Dioxygenases
Neoplasms
Ubiquitin-Protein Ligases
Kidney Neoplasms
Asparagine
Histidine
Proline
Aspartic Acid
Lysine
Phosphotransferases
Amino Acids

Keywords

  • Human Cancer
  • Hydroxylation
  • Hypoxia Inducible Factor alpha
  • Von-Hippel Lindau (VHL)

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

New Insights into Protein Hydroxylation and Its Important Role in Human Diseases. / Zurlo, Giada; Guo, Jianping; Takada, Mamoru; Wei, Wenyi; Zhang, Qing.

In: Biochimica et Biophysica Acta - Reviews on Cancer, Vol. 1866, No. 2, 01.12.2016, p. 208-220.

Research output: Contribution to journalReview article

Zurlo, Giada ; Guo, Jianping ; Takada, Mamoru ; Wei, Wenyi ; Zhang, Qing. / New Insights into Protein Hydroxylation and Its Important Role in Human Diseases. In: Biochimica et Biophysica Acta - Reviews on Cancer. 2016 ; Vol. 1866, No. 2. pp. 208-220.
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