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ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal
Kim, S.H.,Kim, M.O.,Cho, Y.Y.,Yao, K.,Kim, D.J.,Jeong, C.H.,Yu, D.H.,Bae, K.B.,Cho, E.J.,Jung, S.K.,Lee, M.H.,Chen, H.,Kim, J.Y.,Bode, A.M.,Dong, Z. Elsevier 2014 Stem cell research Vol.13 No.1
Nanog regulates human and mouse embryonic stem (ES) cell self-renewal activity. Activation of ERKs signaling negatively regulates ES cell self-renewal and induces differentiation, but the mechanisms are not understood. We found that ERK1 binds and phosphorylates Nanog. Activation of MEK/ERKs signaling and phosphorylation of Nanog inhibit Nanog transactivation, inducing ES cell differentiation. Conversely, suppression of MEK/ERKs signaling enhances Nanog transactivation to inhibit ES cell differentiation. We observed that phosphorylation of Nanog by ERK1 decreases Nanog stability through ubiquitination-mediated protein degradation. Further, we found that this phosphorylation induces binding of FBXW8 with Nanog to reduce Nanog protein stability. Overall, our results demonstrated that ERKs-mediated Nanog phosphorylation plays an important role in self-renewal of ES cells through FBXW8-mediated Nanog protein stability.
Being Adaptive to Pain Enhances Sham Acupuncture Analgesia: A Crossover Healthy Human Study
Zhen Zheng,Dawn Wong Lit Wan,Lars Arendt-Nielsen,Dong Y. Yao,Genevieve Iversen,Charlie C. Xue,Kelun Wang 사단법인약침학회 2017 Journal of Acupuncture & Meridian Studies Vol.10 No.6
We have reported a model that distinguishes pain adaptive individuals (PA) from those who are pain non-adaptive (PNA). The present randomised, cross-over, participant-assessor blinded study aimed to determine the impact of pain adaptability on individuals’ response to real and sham acupuncture. Healthy volunteers (nine PA and 13 PNA) were randomly allocated to receive real and sham acupuncture on the left hand and forearm in two separate acupuncture sessions. Pressure pain thresholds (PPTs) were measured at bilateral forearms and right leg before, immediately after and 20 minutes after the end of acupuncture. Ratings to pinprick and suprathreshold PPT were also recorded. The two groups were comparable in their demographic and baseline data. Analgesia induced by real or sham acupuncture did not differ on any outcome measures. PA responded to acupuncture needling better than PNA, and to sham needling (20% increase in PPT) better than to real acupuncture (7.9%). Those differences were at 20 min after end of acupuncture in the areas distant to the needling sites. PNA reported little changes in PPT. Being adaptive to pain was associated with enhanced distant analgesia in response to sham acupuncture. Our finding might partly explain varied acupuncture analgesia in clinical practice and trials.