Fank1 interacts with Jab1 and regulates cell apoptosis via the AP-1 pathway.
Regulation of apoptosis at various stages of differentiation plays an important role in spermatogenesis. Therefore, the identification and characterisation of highly expressed genes in the testis that are involved in apoptosis is of great value to delineate the mechanism of spermatogenesis. Here, we reported that Fank1, a novel gene highly expressed in testis, functioned as an anti-apoptotic protein that activated the activator protein 1 (AP-1) pathway. We found that Jab1 (Jun activation domain-binding protein 1), a co-activator of AP-1, specifically interacted with Fank1. Reporter analyses showed that Fank1 activated AP-1 pathway in a Jab1-dependent manner. Fank1 overexpression also increased the expression and activation of endogenous c-Jun. Further study showed that Fank1 inhibited cell apoptosis by upregulating and activating endogenous c-Jun and its downstream target, Bcl-3. This process was shown to be Jab1 dependent. Taken together, our results indicated that by interacting with Jab1, Fank1 could suppress cell apoptosis by activating the AP-1-induced anti-apoptotic pathway.
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, 5 Dong Dan San Tiao, Beijing, China.
Hailong
H
Wang
Wei
W
Song
Tinghui
T
Hu
Ning
N
Zhang
Shiying
S
Miao
Shudong
S
Zong
Linfang
L
Wang
D000818:Animals; D017209:Apoptosis; D000081242:B-Cell Lymphoma 3 Protein; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014162:Transfection
D000081242:B-Cell Lymphoma 3 Protein; D000075686:COP9 Signalosome Complex; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C000631344:BCL3 protein, human; C524048:FANK1 protein, human; C501488:COPS5 protein, human