A Negative Feedback Loop Between XBP1 and Fbw7 Regulates Cancer Development

Overview

Journal Oncogenesis

Date 2019 Feb 21

PMID 30783083

Citations 9

Authors

Unbin Chae

Heejin Lee

Bokyung Kim

Haiyoung Jung

Byeong Mo Kim

Ann- Hwee Lee

Dong-Seok Lee

Sang-Hyun Min

Affiliations

Soon will be listed here.

Abstract

In cancer, activation of X-box binding protein (XBP1) has a critical role in tumorigenesis and cancer progression. Transcriptional regulatory mechanism of XBP1 in cancer development has been well known, however, regulation of ubiquitination and degradation of XBP1 has not been elucidated yet. Here we show that Fbw7, a substrate recognition component of the SKP1-Cullin-F-box-type E3 ligase, interacts with XBP1 in a phosphorylation-dependent manner, and facilitates XBP1 ubiquitination and protein degradation. Moreover, Fbw7 inhibits oncogenic pathways including NF-κB, AP1, and Myc induced by XBP1. Interestingly, XBP1 negatively regulates transcription of Fbw7 via a feedback mechanism through NF-κB/E2F-1 axis signaling pathway, suggesting that overexpression of XBP1s may contribute to low level of Fbw7 expression in human cancers. Therefore, a negative feedback loop between Fbw7 and XBP1 contributes to the regulation of tumor development and can be an attractive target for novel therapy in cancers.

Citing Articles

Ubiquitination and Metabolic Disease.

Ma M, Cao R, Tian Y, Fu X Adv Exp Med Biol. 2024; 1466:47-79.

PMID: 39546135 DOI: 10.1007/978-981-97-7288-9_4.

Calcineurin-mediated dephosphorylation stabilizes E2F1 protein by suppressing binding of the FBXW7 ubiquitin ligase subunit.

Sato Y, Habara M, Hanaki S, Masaki T, Tomiyasu H, Miki Y Proc Natl Acad Sci U S A. 2024; 121(41):e2414618121.

PMID: 39361641 PMC: 11474076. DOI: 10.1073/pnas.2414618121.

Pin1-Catalyzed Conformation Changes Regulate Protein Ubiquitination and Degradation.

Jeong J, Usman M, Li Y, Zhou X, Lu K Cells. 2024; 13(9.

PMID: 38727267 PMC: 11083468. DOI: 10.3390/cells13090731.

XBP1 impacts lung adenocarcinoma progression by promoting plasma cell adaptation to the tumor microenvironment.

Zhong Z, Wang J, Han Q, Lin H, Luo H, Guo D Front Genet. 2022; 13:969536.

PMID: 36092910 PMC: 9448868. DOI: 10.3389/fgene.2022.969536.

Roles of XBP1s in Transcriptional Regulation of Target Genes.

Park S, Kang T, So J Biomedicines. 2021; 9(7).

PMID: 34356855 PMC: 8301375. DOI: 10.3390/biomedicines9070791.

References

Wagner E . AP-1--Introductory remarks. Oncogene. 2001; 20(19):2334-5. DOI: 10.1038/sj.onc.1204416. View

Calfon M, Zeng H, Urano F, Till J, Hubbard S, Harding H . IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002; 415(6867):92-6. DOI: 10.1038/415092a. View

Back S, Schroder M, Lee K, Zhang K, Kaufman R . ER stress signaling by regulated splicing: IRE1/HAC1/XBP1. Methods. 2005; 35(4):395-416. DOI: 10.1016/j.ymeth.2005.03.001. View

Nakayama K, Nakayama K . Regulation of the cell cycle by SCF-type ubiquitin ligases. Semin Cell Dev Biol. 2005; 16(3):323-33. DOI: 10.1016/j.semcdb.2005.02.010. View

Welcker M, Clurman B . FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer. 2007; 8(2):83-93. DOI: 10.1038/nrc2290. View

Denis N, Kitzis A, KRUH J, Dautry F, Corcos D . Stimulation of methotrexate resistance and dihydrofolate reductase gene amplification by c-myc. Oncogene. 1991; 6(8):1453-7. View

Shajahan A, Riggins R, Clarke R . The role of X-box binding protein-1 in tumorigenicity. Drug News Perspect. 2009; 22(5):241-6. PMC: 3510657. DOI: 10.1358/dnp.2009.22.5.1378631. View

Wang G, Yang Z, Zhang K . Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res. 2010; 2(1):65-74. PMC: 2826823. View

Lawrence T . The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2010; 1(6):a001651. PMC: 2882124. DOI: 10.1101/cshperspect.a001651. View

10.

He Y, Sun S, Sha H, Liu Z, Yang L, Xue Z . Emerging roles for XBP1, a sUPeR transcription factor. Gene Expr. 2010; 15(1):13-25. PMC: 3374844. DOI: 10.3727/105221610x12819686555051. View

11.

Kurata M, Yamazaki Y, Kanno Y, Ishibashi S, Takahara T, Kitagawa M . Anti-apoptotic function of Xbp1 as an IL-3 signaling molecule in hematopoietic cells. Cell Death Dis. 2011; 2:e118. PMC: 3101701. DOI: 10.1038/cddis.2011.1. View

12.

Schulein C, Eilers M, Popov N . PI3K-dependent phosphorylation of Fbw7 modulates substrate degradation and activity. FEBS Lett. 2011; 585(14):2151-7. DOI: 10.1016/j.febslet.2011.05.036. View

13.

Cheng Y, Li G . Role of the ubiquitin ligase Fbw7 in cancer progression. Cancer Metastasis Rev. 2011; 31(1-2):75-87. DOI: 10.1007/s10555-011-9330-z. View

14.

Mimura N, Fulciniti M, Gorgun G, Tai Y, Cirstea D, Santo L . Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood. 2012; 119(24):5772-81. PMC: 3382937. DOI: 10.1182/blood-2011-07-366633. View

15.

Min S, Lau A, Lee T, Inuzuka H, Wei S, Huang P . Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell. 2012; 46(6):771-83. PMC: 3389221. DOI: 10.1016/j.molcel.2012.04.012. View

16.

Wang Z, Inuzuka H, Zhong J, Wan L, Fukushima H, Sarkar F . Tumor suppressor functions of FBW7 in cancer development and progression. FEBS Lett. 2012; 586(10):1409-18. PMC: 3372850. DOI: 10.1016/j.febslet.2012.03.017. View

17.

Lin W, Chuang Y, Chang Y, Lai M, Teng Y, Su I . Endoplasmic reticulum stress stimulates p53 expression through NF-κB activation. PLoS One. 2012; 7(7):e39120. PMC: 3408479. DOI: 10.1371/journal.pone.0039120. View

18.

Huang H, Ma L, Li J, Yu Y, Zhang D, Wei J . NF-κB1 inhibits c-Myc protein degradation through suppression of FBW7 expression. Oncotarget. 2014; 5(2):493-505. PMC: 3964224. DOI: 10.18632/oncotarget.1643. View

19.

Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt M, Hatziapostolou M . XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway. Nature. 2014; 508(7494):103-107. PMC: 4105133. DOI: 10.1038/nature13119. View

20.

Xia Y, Shen S, Verma I . NF-κB, an active player in human cancers. Cancer Immunol Res. 2014; 2(9):823-30. PMC: 4155602. DOI: 10.1158/2326-6066.CIR-14-0112. View