PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress.
An apoptosis-related protein, cerebral cavernous malformation 3 (CCM3 or PDCD10), has recently been implicated in mutations associated with cerebral cavernous malformation. Herein, we show that PDCD10 interacts with serine/threonine kinase 25 (STK25), an oxidant stress response kinase related to sterile-20 (Ste20) that is activated by oxidative stress and induces apoptotic cell death. Functional investigations indicate that PDCD10 and STK25 protein are up-regulated by H2O2 stimulation, and that co-expression of the proteins accelerates cell apoptosis. The induction of small interfering PDCD10 (siPDCD10) or siSTK25 results in decreased endogenous PDCD10 and STK25 expression, which is accompanied by attenuated cell apoptosis. Interaction between PDCD10 and STK25 modulates ERK activity under oxidative stress. PDCD10 stabilizes STK25 protein through a proteasome-dependent pathway. Our findings suggest that PDCD10 might be a regulatory adaptor required for STK25 functions, which differ distinctly depending on the redox status of the cells that may be potentially related to tumor progression.
Department of Immunology , School of Basic Medical Sciences, Peking University, Beijing, PR China.
Heyu
H
Zhang
Xi
X
Ma
Xuan
X
Deng
Yiyu
Y
Chen
Xiaoning
X
Mo
Yingmei
Y
Zhang
Hongshan
H
Zhao
Dalong
D
Ma
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000099317:Hippo Kinases
D051017:Apoptosis Regulatory Proteins; D006861:Hydrogen Peroxide; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C495390:PDCD10 protein, human; C530660:STK25 protein, human; D000099317:Hippo Kinases