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Updated: Jun 7, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Fank1 interacts with Jab1 and regulates cell apoptosis via the AP-1 pathway
Hailong Wang1, Wei Song, Tinghui Hu
1National 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.
Abstract:
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.
Insights
Novel testis gene Fank1 acts as an anti-apoptotic protein by activating the activator protein 1 (AP-1) pathway. Fank1 interacts with Jab1 to upregulate c-Jun and Bcl-3, suppressing cell apoptosis during spermatogenesis.
Area of Science:
- Reproductive Biology
- Molecular Cell Biology
- Biochemistry
Background:
- Apoptosis regulation is crucial for spermatogenesis.
- Identifying testis-specific genes involved in apoptosis aids understanding of male fertility.
Purpose of the Study:
- To characterize the novel testis-expressed gene Fank1.
- To investigate Fank1's role in apoptosis regulation and spermatogenesis.
Main Methods:
- Gene expression analysis in testis.
- Co-immunoprecipitation to study protein interactions.
- Reporter assays to assess pathway activation.
- Western blotting to evaluate protein levels and activation.
Main Results:
- Fank1 is highly expressed in the testis and functions as an anti-apoptotic protein.
- Fank1 specifically interacts with Jab1 (Jun activation domain-binding protein 1), a co-activator of AP-1.
- Fank1 activates the AP-1 pathway in a Jab1-dependent manner, increasing c-Jun and Bcl-3 expression and activation.
- Fank1 inhibits apoptosis by activating the AP-1 pathway.
Conclusions:
- Fank1 suppresses cell apoptosis through the Jab1-dependent activation of the AP-1 pathway.
- Fank1's interaction with Jab1 is key to its anti-apoptotic function.
- These findings elucidate a novel mechanism regulating apoptosis in spermatogenesis.
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