Marsolier Justine, Weitzman Jonathan B
Sorbonne Paris Cité, université Paris Diderot, UMR7216 CNRS, Épigénétique et destin cellulaire, Laboratoire plasticité des phénotypes cellulaires, 35, rue Hélène Brion, case courrier 7042, 75013 Paris, France.
Med Sci (Paris). 2014 Aug-Sep;30(8-9):772-8. doi: 10.1051/medsci/20143008015. Epub 2014 Sep 1.
Post-translational modifications are critical to modulate protein function. A post-translational mechanism, peptidyl prolyl cis-trans isomerisation, plays a key role in protein regulation. Pin1 is a ubiquitous peptidyl prolyl cis-trans isomerase conserved from Archae to Human. This enzyme binds and isomerizes phospho-serine/threonine-proline motifs. This process can induce conformational change in protein targets and modulates their activity, cellular localization, phosphorylation state, stability and/or protein-protein interactions. Pin1 activity regulates proteins involved in cell proliferation, pluripotency or cellular invasion. Pin1 is overexpressed in several human cancers and contributes to tumorigenesis. Its inactivation constitutes a promising therapeutic strategy.
翻译后修饰对于调节蛋白质功能至关重要。一种翻译后机制，即肽基脯氨酰顺反异构化，在蛋白质调节中起关键作用。Pin1是一种从古细菌到人类都保守存在的普遍存在的肽基脯氨酰顺反异构酶。这种酶结合并异构化磷酸化丝氨酸/苏氨酸-脯氨酸基序。这一过程可诱导蛋白质靶标的构象变化，并调节其活性、细胞定位、磷酸化状态、稳定性和/或蛋白质-蛋白质相互作用。Pin1活性调节参与细胞增殖、多能性或细胞侵袭的蛋白质。Pin1在几种人类癌症中过度表达，并促进肿瘤发生。其失活是一种有前景的治疗策略。
