典型文献
The multifunctional adaptor protein HIP-55 couples Smad7 to accelerate TGF-β type Ⅰ receptor degradation
文献摘要：
Transforming growth factor β(TGF-β)is a multifunctional polypeptide that plays critical roles in regulating a broad range of cellular functions and physiological processes.TGF-β signalling dysfunction contributes to many disorders,such as cardiovascular diseases,cancer and immunological diseases.The homoeostasis of negative feedback regulation is critical for signal robustness,duration and specificity,which precisely control physiological and pathophysiological processes.However,the underlying mechanism by which the negative regulation of TGF-β signalling is integrated and coordinated is still unclear.Here,we reveal that haematopoietic progenitor kinase-interacting protein of 55 kDa(HIP-55)was upregulated upon TGF-β stimulation,while the loss of HIP-55 caused TGF-β signalling overactivation and the abnormal accumulation of downstream extracellular matrix(ECM)genes.HIP-55 interacts with Smad7 and competes with Smad7/Axin complex formation to inhibit the Axin-mediated degradation of Smad7.HIP-55 further couples Smad7 to TβRⅠ but not TβRⅡ,driving TβRⅠ degradation.Altogether,our findings demonstrate a new mechanism by which the effector and negative feedback functions of HIP-55 are coupled and may provide novel strategies for the treatment of TGF-βsignalling-related human diseases.
文献关键词：
中图分类号：
作者姓名：
Yang Sun;Zi-jian Li
作者机构：
Department of Cardiology and Institute of Vascular Medicine,Peking University Third Hospital;Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides,Ministry of Health;Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education;Beijing Key Laboratory of Cardiovascular Receptors Research,Beijing 100191,China
文献出处：
引用格式：
[1]Yang Sun;Zi-jian Li-.The multifunctional adaptor protein HIP-55 couples Smad7 to accelerate TGF-β type Ⅰ receptor degradation)[J].中国药理学报（英文版）,2022(03):634-644
A类：
homoeostasis
B类：
multifunctional,adaptor,protein,HIP,couples,Smad7,accelerate,TGF,type,receptor,degradation,Transforming,growth,polypeptide,that,plays,critical,roles,regulating,broad,range,functions,processes,signalling,dysfunction,contributes,many,disorders,such,cardiovascular,diseases,cancer,immunological,negative,feedback,regulation,robustness,duration,specificity,which,precisely,control,pathophysiological,However,underlying,mechanism,by,integrated,coordinated,still,unclear,Here,reveal,haematopoietic,progenitor,kinase,interacting,kDa,was,upregulated,upon,stimulation,while,loss,caused,overactivation,abnormal,accumulation,downstream,extracellular,matrix,ECM,genes,interacts,competes,Axin,complex,formation,inhibit,mediated,further,not,driving,Altogether,our,findings,demonstrate,new,effector,are,coupled,may,provide,novel,strategies,treatment,related,human
AB值：
0.595389
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