The endoplasmic reticulum plays an extremely important role in the process of cellular protein secretion. The cyclic AMP-responsive element-binding protein 3 (CREB3) transcription factor family is closely associated with the secretion and transport of proteins within the endoplasmic reticulum. As a member of the CREB3 transcription factor family, cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2) stands out as a non-classical sensor within the endoplasmic reticulum. CREB3L2 can detect and regulate endoplasmic reticulum pressure, exert control over the processes of protein transport and secretion, participate in the development of tumor cells, and is also closely linked to the development of certain human tissues and organs. This article aims to review the role of CREB3L2 in tissue development and disease, shedding light on the related mechanisms of CREB3L2 in cancer development. The goal is to provide insights and directions for further analysis of CREB3L2.
Afrin T, Diwan D, Sahawneh K, et al., 2020, Multilevel Regulation of Endoplasmic Reticulum Stress Responses in Plants: Where Old Roads and New Paths Meet. J Exp Bot, 71(5): 1659–1667. https://doi.org/10.1093/jxb/erz487
Doultsinos D, Avril T, Lhomond S, et al., 2017, Control of the Unfolded Protein Response in Health and Disease. SLAS Discovery, 22(7): 787–800. https://doi.org/10.1177/2472555217701685
Lebeaupin C, Vallée D, Hazari Y, et al., 2018, Endoplasmic Reticulum Stress Signalling and the Pathogenesis of Non-Alcoholic Fatty Liver Disease. J Hepatol, 69(4): 927–947. https://doi.org/10.1016/j.jhep.2018.06.008
Hetz C, Zhang K, Kaufman RJ, 2020, Mechanisms, Regulation and Functions of the Unfolded Protein Response. Nat Rev Mol Cell Biol, 21(8): 421–438. https://doi.org/10.1038/s41580-020-0250-z
Ghemrawi R, Khair M, 2020, Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases. Int J Mol Sci, 21(17): 6127. https://doi.org/10.3390/ijms21176127
Howell SH, 2017, When is the Unfolded Protein Response Not the Unfolded Protein Response? Plant Sci, 260: 139–143. https://doi.org/10.1016/j.plantsci.2017.03.014
Wiseman RL, Mesgarzadeh JS, Hendershot LM, 2022, Reshaping Endoplasmic Reticulum Quality Control Through the Unfolded Protein Response. Mol Cell, 82(8): 1477–1491. https://doi.org/10.1016/j.molcel.2022.03.025
Jegal KH, Park SM, Cho SS, et al., 2017, Activating Transcription Factor 6-Dependent Sestrin 2 Induction Ameliorates ER Stress-Mediated Liver Injury. Biochim Biophys Acta Mol Cell Res, 1864(7): 1295–1307. https://doi.org/10.1016/j.bbamcr.2017.04.010
Saito A, Kamikawa Y, Ito T, et al., 2023, p53-Independent Tumor Suppression by Cell-Cycle Arrest via CREB/ATF Transcription Factor OASIS. Cell Rep, 42(5): 112479. https://doi.org/10.1016/j.celrep.2023.112479
Ying Z, Zhai R, McLean NA, et al., 2015, The Unfolded Protein Response and Cholesterol Biosynthesis Link Luman/CREB3 to Regenerative Axon Growth in Sensory Neurons. J Neurosci, 35(43): 14557–14570. https://doi.org/10.1523/JNEUROSCI.0012-15.2015
Wan H, Wang Q, Chen X, et al., 2020, WDR45 Contributes to Neurodegeneration Through Regulation of ER Homeostasis and Neuronal Death. Autophagy, 16(3): 531–547. https://doi.org/ 10.1080/15548627.2019.1630224
Iwamoto H, Matsuhisa K, Saito A, et al., 2015, Promotion of Cancer Cell Proliferation by Cleaved and Secreted Luminal Domains of ER Stress Transducer BBF2H7. PLoS One, 10(5): e0125982. https://doi.org/10.1371/journal.pone.0125982
Hwang J, Qi L, 2018, Quality Control in the Endoplasmic Reticulum: Crosstalk between ERAD and UPR Pathways. Trends Biochem Sci, 43(8): 593–605. https://doi.org/10.1016/j.tibs.2018.06.005
Krshnan L, van de Weijer ML, Carvalho P, 2022, Endoplasmic Reticulum-Associated Protein Degradation. Cold Spring Harb Perspect Biol, 14(12): a041247. https://doi.org/10.1101/cshperspect.a041247
Kumar V, Maity S, 2021, ER Stress-Sensor Proteins and ER-Mitochondrial Crosstalk-Signaling Beyond (ER) Stress Response. Biomolecules, 11(2): 173. https://doi.org/10.3390/biom11020173
Guillemyn B, Kayserili H, Demuynck L, et al., 2019, A Homozygous Pathogenic Missense Variant Broadens the Phenotypic and Mutational Spectrum of CREB3L1-Related Osteogenesis Imperfecta. Hum Mol Genet, 28(11): 1801–1809. https://doi.org/10.1093/hmg/ddz017
Scheer M, Vokuhl C, Veit-Friedrich I, et al., 2020, Low-Grade Fibromyxoid Sarcoma: A Report of the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr Blood Cancer, 67(2): e28009. https://doi.org/10.1002/pbc.28009
Zeng B, Sun Z, Zhao Q, et al., 2021, SEC23A Inhibit Melanoma Metastatic through Secretory PF4 Cooperation with SPARC to Inhibit MAPK Signaling Pathway. Int J Biol Sci, 17(12): 3000–3012. https://doi.org/10.7150/ijbs.60866
Zheng Z-G, Zhu S-T, Cheng H-M, et al., 2021, Discovery of a Potent SCAP Degrader that Ameliorates HFD-Induced Obesity, Hyperlipidemia and Insulin Resistance via an Autophagy-Independent Lysosomal Pathway. Autophagy, 17(7): 1592–1613. https://doi.org/10.1080/15548627.2020.1757955
Kamikawa Y, Saito A, Matsuhisa K, et al., 2021, OASIS/CREB3L1 is a Factor that Responds to Nuclear Envelope Stress. Cell Death Discov, 7(1): 152. https://doi.org/10.1038/s41420-021-00540-x
Aibar S, González-Blas CB, Moerman T, et al., 2017, SCENIC: Single-Cell Regulatory Network Inference and Clustering. Nat Methods, 14(11): 1083–1086. https://doi.org/10.1038/nmeth.4463
Saito A, Hino S, Murakami T, et al., 2009, Regulation of Endoplasmic Reticulum Stress Response by a BBF2H7-Mediated Sec23a Pathway is Essential for Chondrogenesis. Nat Cell Biol, 11(10): 1197–1204. https://doi.org/10.1038/ncb1962
Yumimoto K, Matsumoto M, Onoyama I, et al., 2013, F-Box and WD Repeat Domain-Containing-7 (Fbxw7) Protein Targets Endoplasmic Reticulum-Anchored Osteogenic and Chondrogenic Transcriptional Factors for Degradation. J Biol Chem, 288(40): 28488–28502. https://doi.org/10.1074/jbc.M113.465179
Ishikura-Kinoshita S, Saeki H, Tsuji-Naito K, 2012, BBF2H7-Mediated Sec23A Pathway is Required for Endoplasmic Reticulum-to-Golgi Trafficking in Dermal Fibroblasts to Promote Collagen Synthesis. J Invest Dermatol,132(8): 2010–2018. https://doi.org/10.1038/jid.2012.103
Hino K, Saito A, Kido M, et al., 2014, Master Regulator for Chondrogenesis, Sox9, Regulates Transcriptional Activation of the Endoplasmic Reticulum Stress Transducer BBF2H7/CREB3L2 in Chondrocytes. J Biol Chem, 289(20): 13810–13820. https://doi.org/10.1074/jbc.M113.543322
Williams CM, Du W, Mangano WE, et al., 2021, Mediastinal Low-Grade Fibromyxoid Sarcoma With FUSCREB3L2Gene Fusion. Cureus, 13(6): e15606. https://doi.org/10.7759/cureus.15606
Hu Y, Chu L, Liu J, et al., 2019, Knockdown of CREB3 Activates Endoplasmic Reticulum Stress and Induces Apoptosis in Glioblastoma. Aging (Albany NY), 11(19): 8156–8168. https://doi.org/10.18632/aging.102310
Tabrizian N, Nouruzi S, Cui CJ, et al., 2023, ASCL1 is Activated Downstream of the ROR2/CREB Signaling Pathway to Support Lineage Plasticity in Prostate Cancer. Cell Rep, 42(8): 112937. https://doi.org/10.1016/j.celrep.2023.112937
Chen X, Cubillos-Ruiz JR, 2021, Endoplasmic Reticulum Stress Signals in the Tumour and Its Microenvironment. Nat Rev Cancer, 21(2): 71–88. https://doi.org/10.1038/s41568-020-00312-2
Chen Y, Liu Y, Lin S, et al., 2017, Identification of Novel SCIRR69-Interacting Proteins During ER Stress Using SILAC-Immunoprecipitation Quantitative Proteomics Approach. Neuromolecular Med, 19(1): 81–93. https://doi.org/10.1007/s12017-016-8431-9
Greenwood MP, Greenwood M, Gillard BT, et al., 2017, Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1. Front Mol Neurosci, 10: 413. https://doi.org/10.3389/fnmol.2017.00413
Al-Maskari M, Care MA, Robinson E, et al., 2018, Site-1 Protease Function is Essential for the Generation of Antibody Secreting Cells and Reprogramming for Secretory Activity. Sci Rep, 8(1): 14338. https://doi.org/10.1038/s41598-018-32705-7
Chen G, Tang Q, Yu S, et al., 2023, Developmental Growth Plate Cartilage Formation Suppressed by Artificial Light at Night via Inhibiting BMAL1-Driven Collagen Hydroxylation. Cell Death Differ, 30(6): 1503–1516. https://doi.org/10.1038/s41418-023-01152-x
Huang W, Ji R, Ge S, et al., 2021, MicroRNA-92b-3p Promotes the Progression of Liver Fibrosis by Targeting CREB3L2 through the JAK/STAT Signaling Pathway. Pathol Res Pract, 219: 153367. https://doi.org/10.1016/j.prp.2021.153367
Owusu-Akyaw A, Krishnamoorthy K, Goldsmith LT, et al., 2019, The Role of Mesenchymal-Epithelial Transition in Endometrial Function. Hum Reprod Update, 25(1): 114–133. https://doi.org/10.1093/humupd/dmy035
Hu L, Chen X, Narwade N, et al., 2021, Single-Cell Analysis Reveals Androgen Receptor Regulates the ER-to-Golgi Trafficking Pathway with CREB3L2 to Drive Prostate Cancer Progression. Oncogene, 40(47): 6479–6493. https://doi.org/10.1038/s41388-021-02026-7
Roque CG, Chung KM, McCurdy EP, et al., 2023, CREB3L2-ATF4 Heterodimerization Defines a Transcriptional Hub of Alzheimer’s Disease Gene Expression Linked to Neuropathology. Sci Adv, 9(9): eadd2671. https://doi.org/10.1126/sciadv.add2671