The human WW45 protein enhances MST1-mediated apoptosis in vivo.
Mammalian sterile 20-like kinase 1 (MST1) is a serine/threonine protein kinase that is activated in response to a variety of apoptotic stimuli and causes apoptosis when over-expressed in mammalian cells. The physiological regulation and cellular targets of MST1 are not well understood. Using a yeast two-hybrid system, we identified human WW45 (hWW45, also called hSav1) as an MST1-binding protein. The association between the two proteins was confirmed by immunofluorescence and co-immunoprecipitation, and hWW45 was present in both the cytoplasm and nucleus. When hWW45 alone was over-expressed, it weakly induced apoptosis. However, hWW45 augmented MST1-induced apoptosis when the two were co-expressed. Conversely, RNA interference-mediated depletion of endogenous hWW45 suppressed MST1-induced apoptosis. These results indicate that hWW45 is required to enhance MST1-mediated apoptosis in vivo and thus is a critical player in an MST1-driven cell death signaling pathway.
Luo
Xuelai
X
Department of Surgery and Institute of Cancer Research, Tongji Hospital, Wuhan 430030, PR China.
Li
Zhaoming
Z
Yan
Qun
Q
Li
Xiaolan
X
Tao
Deding
D
Wang
Jing
J
Leng
Yan
Y
Gardner
Kevin
K
Judge
Susan I V
SI
Li
Qingdi Q
QQ
Hu
Junbo
J
Gong
Jianping
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D041681:NIH 3T3 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D000099317:Hippo Kinases
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C415864:SAV1 protein, human; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases; C095566:STK4 protein, human