Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors
The Sec61 complex, which is located on the membrane of the mammalian endoplasmic reticulum (ER), serves as a pivotal component of protein transport channels. It plays a central role in the transport of nascent peptides and precursor peptides to the ER. This process includes the directed movement of...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1580086/full |
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| author | Jingxin Xin Jingxin Xin Jingxin Xin Jingxin Xin Jingxin Xin Keling Yin Keling Yin Keling Yin Keling Yin Keling Yin Shimeng Li Shimeng Li Shimeng Li Shimeng Li Shimeng Li Peiyuan Gu Peiyuan Gu Peiyuan Gu Peiyuan Gu Peiyuan Gu Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao |
| author_facet | Jingxin Xin Jingxin Xin Jingxin Xin Jingxin Xin Jingxin Xin Keling Yin Keling Yin Keling Yin Keling Yin Keling Yin Shimeng Li Shimeng Li Shimeng Li Shimeng Li Shimeng Li Peiyuan Gu Peiyuan Gu Peiyuan Gu Peiyuan Gu Peiyuan Gu Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao |
| author_sort | Jingxin Xin |
| collection | DOAJ |
| description | The Sec61 complex, which is located on the membrane of the mammalian endoplasmic reticulum (ER), serves as a pivotal component of protein transport channels. It plays a central role in the transport of nascent peptides and precursor peptides to the ER. This process includes the directed movement of precursor peptides to the ER membrane and the opening of the Sec61 transduction channel for translocation. The Sec61 channel not only plays a key role in transporting peptides into cells but also acts as a passive ER Ca2+ leak channel. In addition, the mutation, amplification and overexpression of Sec genes are closely related to the development of various genetic diseases and cancers. Over the past few decades, studies have elucidated the function of the Sec61 protein in the pathogenesis of diseases such as cancer, and Sec61 inhibitors have been developed for their treatment. This review describes the structure of Sec61 and its function in transporting ER transmembrane proteins and further summarizes the role of this gene in disease and recent advancements in Sec61 inhibitors. This study provides novel insights into the involvement of Sec61 in disease etiology and lays the groundwork for future treatment modalities targeting this pivotal protein complex. |
| format | Article |
| id | doaj-art-e86905755f25455f88d58d94e456823a |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-e86905755f25455f88d58d94e456823a2025-08-20T03:19:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15800861580086Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitorsJingxin Xin0Jingxin Xin1Jingxin Xin2Jingxin Xin3Jingxin Xin4Keling Yin5Keling Yin6Keling Yin7Keling Yin8Keling Yin9Shimeng Li10Shimeng Li11Shimeng Li12Shimeng Li13Shimeng Li14Peiyuan Gu15Peiyuan Gu16Peiyuan Gu17Peiyuan Gu18Peiyuan Gu19Shanshan Shao20Shanshan Shao21Shanshan Shao22Shanshan Shao23Shanshan Shao24Shanshan Shao25Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, ChinaShandong Key Laboratory of Endocrine Metabolism and Aging, Jinan, Shandong, ChinaShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China“Chuangxin China” Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, ChinaShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaShandong Key Laboratory of Endocrine Metabolism and Aging, Jinan, Shandong, ChinaShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China“Chuangxin China” Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, ChinaShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, ChinaShandong Key Laboratory of Endocrine Metabolism and Aging, Jinan, Shandong, ChinaShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China“Chuangxin China” Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, ChinaShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaShandong Key Laboratory of Endocrine Metabolism and Aging, Jinan, Shandong, ChinaShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China“Chuangxin China” Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, ChinaShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaShandong Key Laboratory of Endocrine Metabolism and Aging, Jinan, Shandong, ChinaShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China“Chuangxin China” Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, Jinan, Shandong, ChinaShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, ChinaThe Sec61 complex, which is located on the membrane of the mammalian endoplasmic reticulum (ER), serves as a pivotal component of protein transport channels. It plays a central role in the transport of nascent peptides and precursor peptides to the ER. This process includes the directed movement of precursor peptides to the ER membrane and the opening of the Sec61 transduction channel for translocation. The Sec61 channel not only plays a key role in transporting peptides into cells but also acts as a passive ER Ca2+ leak channel. In addition, the mutation, amplification and overexpression of Sec genes are closely related to the development of various genetic diseases and cancers. Over the past few decades, studies have elucidated the function of the Sec61 protein in the pathogenesis of diseases such as cancer, and Sec61 inhibitors have been developed for their treatment. This review describes the structure of Sec61 and its function in transporting ER transmembrane proteins and further summarizes the role of this gene in disease and recent advancements in Sec61 inhibitors. This study provides novel insights into the involvement of Sec61 in disease etiology and lays the groundwork for future treatment modalities targeting this pivotal protein complex.https://www.frontiersin.org/articles/10.3389/fphar.2025.1580086/fullSec61endoplasmic reticulumgenetic diseasetumorinhibitor |
| spellingShingle | Jingxin Xin Jingxin Xin Jingxin Xin Jingxin Xin Jingxin Xin Keling Yin Keling Yin Keling Yin Keling Yin Keling Yin Shimeng Li Shimeng Li Shimeng Li Shimeng Li Shimeng Li Peiyuan Gu Peiyuan Gu Peiyuan Gu Peiyuan Gu Peiyuan Gu Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Shanshan Shao Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors Frontiers in Pharmacology Sec61 endoplasmic reticulum genetic disease tumor inhibitor |
| title | Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors |
| title_full | Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors |
| title_fullStr | Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors |
| title_full_unstemmed | Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors |
| title_short | Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors |
| title_sort | exploring the er channel protein sec61 recent advances in pathophysiological significance and novel pharmacological inhibitors |
| topic | Sec61 endoplasmic reticulum genetic disease tumor inhibitor |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1580086/full |
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