New Insights into Protein Hydroxylation and Its Important Role in Human Diseases.
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.
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Giada
G
Zurlo
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Jianping
J
Guo
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Mamoru
M
Takada
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: wwei2@bidmc.harvard.edu.
Wenyi
W
Wei
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: Qing_Zhang@med.unc.edu.
Qing
Q
Zhang
D000818:Animals; D006801:Humans; D006900:Hydroxylation; D064828:Prolyl Hydroxylases / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D064828:Prolyl Hydroxylases
Human Cancer; Hydroxylation; Hypoxia Inducible Factor alpha; Von-Hippel Lindau (VHL)
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