Peptidyl-Prolyl Isomerase Pin1: A Novel Target for Cancer Therapy
Pp. 226-263 (38)
Rohit Mathur, Anant N. Bhatt, Seema Gupta and Bilikere S. Dwarakanath
Phosphorylation and post-phosphorylation events are important regulators of
cell signaling and protein activity. Important information about the peptidyl-prolyl
isomerase Pin1 in the last decade has revealed a level of regulation beyond
phosphorylation. Pin1 can interact with phosphorylated proteins and alter the
isomerization state of the peptide bond involving serine/threonine-proline, which can
bring about a change in their structure. Post-phosphorylation events, such as
isomerization of the peptide bond, can lead to functional consequences e.g. increase in
protein activity, turnover, dephosphorylation and ubiquitination on account of changes
to the protein structure. Since levels of Pin1 are higher in tumor cells than in normal
cells, Pin1 appears to be an attractive target for cancer therapy. Indeed, many studies
have suggested that Pin1 inhibition could induce tumor cell death. The current literature
and insights into use of Pin1 inhibitors as anti-cancer therapeutic agents and as
adjuvants are reviewed.
Pin1, post-phosphorylation, isomerization, DNA damage response,
drug resistance, apoptosis, cancer, cell death, new drug targets, drug design,
enzyme inhibitors, PPIase, peptidyl-prolyl isomerase.
Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India.