Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2-independent nuclear YAP localization. Exp Cell Res 2017 Dec 01;361(1):93-100
Date
10/12/2017Pubmed ID
29017756DOI
10.1016/j.yexcr.2017.10.006Scopus ID
2-s2.0-85031324939 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells. To this end, cells were subjected to 2.5% static equiaxial strain for different time periods. Western blot and fluorescence imaging-based analyses revealed a clear modulation of nuclear YAP localization. This modulation fairly coincided with the altered course of the KI-67 protein amount in conjunction with the percentage of KI-67-positive and thus proliferating cells. The inhibition of the ERK1/2 activity via U0126 yielded an unchanged strain-related modulation of nuclear YAP localization, while YAP amount in whole cell extracts of strained cells was decreased. Administration of the YAP-inhibiting drug Verteporfin evoked a clear reduction of KI-67-positive and thus proliferating cells by approximately 65%, irrespective of strain. Our data reveal YAP as a regulator of strain-modulated proliferation which occurs in a MAPK-independent fashion.
Author List
Hülter-Hassler D, Wein M, Schulz SD, Proksch S, Steinberg T, Jung BA, Tomakidi PAuthor
Melissa Wein MD Assistant Professor in the Radiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingBiomechanical Phenomena
Cell Nucleus
Cell Proliferation
Cells, Cultured
Humans
Male
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Periodontal Ligament
Phosphoproteins
Protein Transport
Transcription Factors
