Characterization of Hippo Pathway Components by Gene Inactivation

被引:226
作者
Plouffe, Steven W. [1 ,2 ]
Meng, Zhipeng [1 ,2 ]
Lin, Kimberly C. [1 ,2 ]
Lin, Brian [1 ,2 ]
Hong, Audrey W. [1 ,2 ]
Chun, Justin V. [1 ,2 ]
Guan, Kun-Liang [1 ,2 ]
机构
[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA
关键词
TUMOR-SUPPRESSOR; CELL-PROLIFERATION; SIGNALING PATHWAY; YAP ONCOPROTEIN; GROWTH-CONTROL; TISSUE-GROWTH; SIZE-CONTROL; HUMAN CANCER; KINASES; DROSOPHILA;
D O I
10.1016/j.molcel.2016.10.034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well under-stood how the Hippo pathway becomesdysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ. To provide an overview of important Hippo pathway components, we created knockout cell lines for many of these components and compared their relative contributions to YAP/TAZ regulation in response to a wide range of physiological signals. By this approach, we provide an overview of the functional importance of many Hippo pathway components and demonstrate NF2 and RHOA as important regulators of YAP/TAZ and TAOK1/3 as direct kinases for LATS1/2.
引用
收藏
页码:993 / 1008
页数:16
相关论文
共 42 条
[21]   Disease implications of the Hippo/YAP pathway [J].
Plouffe, Steven W. ;
Hong, Audrey W. ;
Guan, Kun-Liang .
TRENDS IN MOLECULAR MEDICINE, 2015, 21 (04) :212-222
[22]   The Sterile 20-like Kinase Tao-1 Controls Tissue Growth by Regulating the Salvador-Warts-Hippo Pathway [J].
Poon, Carole L. C. ;
Lin, Jane I. ;
Zhang, Xiaomeng ;
Harvey, Kieran F. .
DEVELOPMENTAL CELL, 2011, 21 (05) :896-906
[23]   MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation [J].
Praskova, Maria ;
Xia, Fan ;
Avruch, Joseph .
CURRENT BIOLOGY, 2008, 18 (05) :311-321
[24]   A neuronal function of the tumor suppressor protein merlin [J].
Schulz, Alexander ;
Zoch, Ansgar ;
Morrison, Helen .
ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2014, 2
[25]   The Neurofibromatosis 2 Tumor Suppressor Gene Product, Merlin, Regulates Human Meningioma Cell Growth by Signaling through YAP [J].
Striedinger, Katherine ;
VandenBerg, Scott R. ;
Baia, Gilson S. ;
McDermott, Michael W. ;
Gutmann, David H. ;
Lal, Anita .
NEOPLASIA, 2008, 10 (11) :1204-1212
[26]   A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome [J].
Sultan, Marc ;
Schulz, Marcel H. ;
Richard, Hugues ;
Magen, Alon ;
Klingenhoff, Andreas ;
Scherf, Matthias ;
Seifert, Martin ;
Borodina, Tatjana ;
Soldatov, Aleksey ;
Parkhomchuk, Dmitri ;
Schmidt, Dominic ;
O'Keeffe, Sean ;
Haas, Stefan ;
Vingron, Martin ;
Lehrach, Hans ;
Yaspo, Marie-Laure .
SCIENCE, 2008, 321 (5891) :956-960
[27]   salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines [J].
Tapon, N ;
Harvey, KF ;
Bell, DW ;
Wahrer, DCR ;
Schiripo, TA ;
Haber, DA ;
Hariharan, IK .
CELL, 2002, 110 (04) :467-478
[28]   AMPK modulates Hippo pathway activity to regulate energy homeostasis [J].
Wang, Wenqi ;
Xiao, Zhen-Dong ;
Li, Xu ;
Aziz, Kathryn E. ;
Gan, Boyi ;
Johnson, Randy L. ;
Chen, Junjie .
NATURE CELL BIOLOGY, 2015, 17 (04) :490-+
[29]   Angiomotin-like Proteins Associate with and Negatively Regulate YAP1 [J].
Wang, Wenqi ;
Huang, Jun ;
Chen, Junjie .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (06) :4364-4370
[30]   Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer [J].
Wang, Xiaodan ;
Su, Lili ;
Ou, Qishui .
EUROPEAN JOURNAL OF CANCER, 2012, 48 (08) :1227-1234