The Roles of KLHL Family Members in Human Cancers

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2022 Dec 12

PMID 36504893

Authors

Ganghui Ye

Jie Wang

Weili Yang

JinYun Li

Meng Ye

Xiaofeng Jin

Affiliations

Soon will be listed here.

Abstract

The Kelch-like (KLHL) family members consist of three domains: bric-a-brac, tramtrack, broad complex/poxvirus and zinc finger domain, BACK domain and Kelch domain, which combine and interact with Cullin3 to form an E3 ubiquitin ligase. Research has indicated that KLHL family members ubiquitinate target substrates to regulate physiological and pathological processes, including tumorigenesis and progression. KLHL19, a member of the KLHL family, is associated with tumorigenesis and drug resistance. However, the regulation and cross talks of other KLHL family members, which also play roles in cancer, are still unclear. Our review mainly explores studies concerning the roles of other KLHL family members in tumor-related regulation to provide novel insights into KLHL family members.

Citing Articles

The Cullin3-Rbx1-KLHL9 E3 ubiquitin ligase complex ubiquitinates Rheb and supports amino acid-induced mTORC1 activation.

Yao Y, Hong S, Yoshida S, Swaroop V, Curtin B, Inoki K Cell Rep. 2024; 44(1):115101.

PMID: 39708321 PMC: 11844325. DOI: 10.1016/j.celrep.2024.115101.

Allelic effects on expression likely mediated by JunB/D underlie a PDAC GWAS signal at chr1p36.33.

Connelly K, Hullin K, Abdolalizadeh E, Zhong J, Eiser D, OBrien A medRxiv. 2024; .

PMID: 39371158 PMC: 11451706. DOI: 10.1101/2024.09.16.24313748.

KLHL14 is a tumor suppressor downregulated in undifferentiated thyroid cancer.

Esposito M, Migliaccio A, Credendino S, Maturi R, Prevete N, De Vita G Cell Death Discov. 2024; 10(1):297.

PMID: 38909024 PMC: 11193815. DOI: 10.1038/s41420-024-02063-7.

Characterization of KLHL14 anti-oncogenic action in malignant mesothelioma.

Canciello A, Benot Dominguez R, Barboni B, Giordano A, Morrione A Heliyon. 2024; 10(6):e27731.

PMID: 38509883 PMC: 10950656. DOI: 10.1016/j.heliyon.2024.e27731.

Structural and biochemical characterization establishes a detailed understanding of KEAP1-CUL3 complex assembly.

Adamson R, Payne N, Bartual S, Mazitschek R, Bullock A Free Radic Biol Med. 2023; 204:215-225.

PMID: 37156295 PMC: 10564622. DOI: 10.1016/j.freeradbiomed.2023.04.021.

References

Kaplan Y, Gibbs-Bar L, Kalifa Y, Feinstein-Rotkopf Y, Arama E . Gradients of a ubiquitin E3 ligase inhibitor and a caspase inhibitor determine differentiation or death in spermatids. Dev Cell. 2010; 19(1):160-73. DOI: 10.1016/j.devcel.2010.06.009. View

Tecalco-Cruz A, Ramirez-Jarquin J, Cruz-Ramos E . Estrogen Receptor Alpha and its Ubiquitination in Breast Cancer Cells. Curr Drug Targets. 2018; 20(6):690-704. DOI: 10.2174/1389450119666181015114041. View

Juan W, Hong W . Targeting the Hippo Signaling Pathway for Tissue Regeneration and Cancer Therapy. Genes (Basel). 2016; 7(9). PMC: 5042386. DOI: 10.3390/genes7090055. View

Hernandez M, Andres-Barquin P, Holt I, Israel M . Cloning of human ENC-1 and evaluation of its expression and regulation in nervous system tumors. Exp Cell Res. 1998; 242(2):470-7. DOI: 10.1006/excr.1998.4109. View

Jin L, Pahuja K, Wickliffe K, Gorur A, Baumgartel C, Schekman R . Ubiquitin-dependent regulation of COPII coat size and function. Nature. 2012; 482(7386):495-500. PMC: 3292188. DOI: 10.1038/nature10822. View

Yip H, Chopra R, Chakrabarti R, Veena M, Ramamurthy B, Srivatsan E . Cisplatin-induced growth arrest of head and neck cancer cells correlates with increased expression of p16 and p53. Arch Otolaryngol Head Neck Surg. 2006; 132(3):317-26. DOI: 10.1001/archotol.132.3.317. View

Fan S, Wang Y, Sheng N, Xie Y, Lu J, Zhang Z . Low expression of ENC1 predicts a favorable prognosis in patients with ovarian cancer. J Cell Biochem. 2018; 120(1):861-871. DOI: 10.1002/jcb.27447. View

Lear T, Lockwood K, Larsen M, Tuncer F, Kennerdell J, Morse C . Kelch-like protein 42 is a profibrotic ubiquitin E3 ligase involved in systemic sclerosis. J Biol Chem. 2020; 295(13):4171-4180. PMC: 7105301. DOI: 10.1074/jbc.AC119.012066. View

Zhang C, Liu J, Huang G, Zhao Y, Yue X, Wu H . Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Genes Dev. 2016; 30(17):1956-70. PMC: 5066239. DOI: 10.1101/gad.283283.116. View

10.

Young R, Shaffer 3rd A, Phelan J, Staudt L . B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 2015; 52(2):77-85. PMC: 4374122. DOI: 10.1053/j.seminhematol.2015.01.008. View

11.

Beck J, Maerki S, Posch M, Metzger T, Persaud A, Scheel H . Ubiquitylation-dependent localization of PLK1 in mitosis. Nat Cell Biol. 2013; 15(4):430-9. PMC: 7116173. DOI: 10.1038/ncb2695. View

12.

Bernatik O, Paclikova P, Sri Ganji R, Bryja V . Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled. Cells. 2020; 9(5). PMC: 7290506. DOI: 10.3390/cells9051147. View

13.

Yuan W, Lee Y, Lin S, Chang L, Tan Y, Hung C . K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking. Mol Cell. 2014; 54(4):586-600. DOI: 10.1016/j.molcel.2014.03.035. View

14.

Sumara I, Peter M . A Cul3-based E3 ligase regulates mitosis and is required to maintain the spindle assembly checkpoint in human cells. Cell Cycle. 2007; 6(24):3004-10. DOI: 10.4161/cc.6.24.5068. View

15.

Perri F, Pisconti S, Della Vittoria Scarpati G . P53 mutations and cancer: a tight linkage. Ann Transl Med. 2017; 4(24):522. PMC: 5233470. DOI: 10.21037/atm.2016.12.40. View

16.

Song M, Lee D, Chun K, Kim E . The Role of NRF2/KEAP1 Signaling Pathway in Cancer Metabolism. Int J Mol Sci. 2021; 22(9). PMC: 8122702. DOI: 10.3390/ijms22094376. View

17.

Niture S, Jaiswal A . INrf2 (Keap1) targets Bcl-2 degradation and controls cellular apoptosis. Cell Death Differ. 2010; 18(3):439-51. PMC: 3010499. DOI: 10.1038/cdd.2010.114. View

18.

Bar-Peled L, Chantranupong L, Cherniack A, Chen W, Ottina K, Grabiner B . A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013; 340(6136):1100-6. PMC: 3728654. DOI: 10.1126/science.1232044. View

19.

Pons B, Peg V, Vazquez-Sanchez M, Lopez-Vicente L, Argelaguet E, Coch L . The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model. Int J Oncol. 2011; 39(5):1337-45. DOI: 10.3892/ijo.2011.1118. View

20.

Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V . XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996; 86(3):391-9. DOI: 10.1016/s0092-8674(00)80112-9. View