CSE1L, also known as Cellular Apoptosis Susceptibility (CAS), is a multiple-functional protein. It is involved in various biological processes such as apoptosis, cell survival, chromosome assembly, nucleocytoplasmic transport, and microvesicle formation [5]. It is associated with the Ras/RAF/MAPK/ERK signaling pathways, and its phosphorylation is regulated by the extracellular signal-regulated kinase (ERK) [5]. CSE1L is located on chromosome 20q13, a locus often amplified in cancers [4].

CSE1L has been found to play crucial roles in multiple disease conditions. In acute lung injury, the marine alkaloid naamidine J was shown to interact with CSE1L, inhibiting the nuclear translocation and transcriptional activity of transcription factor SP1, thus suppressing inflammation in macrophages and ameliorating acute lung injury [1]. In lung cancer, knockdown of CSE1L impaired cell proliferation, invasion, migration, and induced apoptosis, potentially affecting tumor progression through the MET/STAT3/PD-L1 signaling [2]. In seminoma, CSE1L was significantly enriched, and its knockdown attenuated cell proliferative capacity, with cells mainly arrested in the G0/G1 phase and moderately delayed in the G2/M phase [3]. In acute myeloid leukemia, CSE1L silencing enhanced cytarabine-mediated cytotoxicity, promoting caspase-3 and caspase-9 protein expression and apoptosis, and reducing the expression levels of p-JKA2 and p-STAT3 proteins [6].

In conclusion, CSE1L is a key protein involved in multiple biological processes and is associated with various diseases, especially cancers. Studies using knockdown or silencing (functionally similar to loss-of-function in KO models) have revealed its roles in inflammation regulation in acute lung injury and tumor progression in different cancers, highlighting its potential as a therapeutic target for these diseases.

References:

1. Gao, Cheng-Long, Song, Jin-Qian, Yang, Ze-Nan, Pang, Tao, Li, Xu-Wen. 2024. Chemoproteomics of Marine Natural Product Naamidine J Unveils CSE1L as a Therapeutic Target in Acute Lung Injury. In Journal of the American Chemical Society, 146, 28384-28397. doi:10.1021/jacs.4c09695. https://pubmed.ncbi.nlm.nih.gov/39324953/

2. Liu, Weijun, Zhou, Zhiqing, Li, Yu, He, Yanli, Chen, Guoan. 2021. CSE1L silencing impairs tumor progression via MET/STAT3/PD-L1 signaling in lung cancer. In American journal of cancer research, 11, 4380-4393. doi:. https://pubmed.ncbi.nlm.nih.gov/34659893/

3. Liu, Chunyan, Wei, Jiajing, Xu, Kang, Zhang, Huiping, Xiong, Chengliang. 2018. CSE1L participates in regulating cell mitosis in human seminoma. In Cell proliferation, 52, e12549. doi:10.1111/cpr.12549. https://pubmed.ncbi.nlm.nih.gov/30485574/

4. Behrens, P, Brinkmann, U, Wellmann, A. . CSE1L/CAS: its role in proliferation and apoptosis. In Apoptosis : an international journal on programmed cell death, 8, 39-44. doi:. https://pubmed.ncbi.nlm.nih.gov/12510150/

5. Jiang, Ming-Chung. 2016. CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 13077-13090. doi:. https://pubmed.ncbi.nlm.nih.gov/27596143/

6. Liu, Xiaoyu, Yang, Lin, Guan, Kunping, Chen, Zhen, Yang, Hua. 2024. CSE1L Silencing Enhances Cytarabine-mediated Cytotoxicity in Acute Myeloid Leukemia. In Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion, 40, 629-637. doi:10.1007/s12288-024-01773-3. https://pubmed.ncbi.nlm.nih.gov/39469152/