CYLD negatively regulates transforming growth factor-beta-signalling via deubiquitinating Akt

Title
CYLD negatively regulates transforming growth factor-beta-signalling via deubiquitinating Akt
Author(s)
임재향[임재향]히로푸미 조노[히로푸미 조노]켄세이 코마츠[켄세이 코마츠]우창훈이지윤[이지윤]마사노리 미야타[마사노리 미야타]타카시 마츠노[타카시 마츠노]생빈 수[생빈 수]유센 황[유센 황]웬홍 장[웬홍 장]박수현[박수현]김유일[김유일]최유덕[최유덕]허경선[허경선]하오동 수[하오동 수]파트리시아 본[파트리시아 본]토모아키 코가[토모아키 코가]하이동 수[하이동 수]첸 얀[첸 얀]빈 왕[빈 왕]린펑 첸[린펑 첸]신화 펑[신화 펑]젠동 리[젠동 리]
Keywords
NF-KAPPA-B; TGF-BETA; PULMONARY-FIBROSIS; LUNG INJURY; MUCIN TRANSCRIPTION; CROSS-TALK; NULL MICE; P38 MAPK; SMAD3; ACTIVATION
Issue Date
201204
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE COMMUNICATIONS, v.3
Abstract
Lung injury, whether induced by infection or caustic chemicals, initiates a series of complex wound-healing responses. If uncontrolled, these responses may lead to fibrotic lung diseases and loss of function. Thus, resolution of lung injury must be tightly regulated. The key regulatory proteins required for tightly controlling the resolution of lung injury have yet to be identified. Here we show that loss of deubiquitinase CYLD led to the development of lung fibrosis in mice after infection with Streptococcus pneumoniae. CYLD inhibited transforming growth factor-beta-signalling and prevented lung fibrosis by decreasing the stability of Smad3 in an E3 ligase carboxy terminus of Hsc70-interacting protein-dependent manner. Moreover, CYLD decreases Smad3 stability by deubiquitinating K63-polyubiquitinated Akt. Together, our results unveil a role for CYLD in tightly regulating the resolution of lung injury and preventing fibrosis by deubiquitinating Akt. These studies may help develop new therapeutic strategies for preventing lung fibrosis.
URI
http://hdl.handle.net/YU.REPOSITORY/28581http://dx.doi.org/10.1038/ncomms1776
ISSN
2041-1723
Appears in Collections:
의과대학 > 약리학교실 > Articles
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