The RING domain in the anti-apoptotic protein XIAP stabilizes c-Myc protein and preserves anchorage-independent growth of bladder cancer cells.

The Journal of Biological Chemistry
Guosong JiangChuanshu Huang

Abstract

X-linked inhibitor of apoptosis protein (XIAP) suppresses apoptosis and plays key roles in the development, growth, migration, and invasion of cancer cells. Therefore, XIAP has recently attracted much attention as a potential antineoplastic therapeutic target, requiring elucidation of the molecular mechanisms underlying its biological activities. Here, using shRNA-mediated gene silencing, immunoblotting, quantitative RT-PCR, anchorage-independent growth assay, and invasive assay, we found that XIAP's RING domain, but not its BIR domain, is crucial for XIAP-mediated up-regulation of c-Myc protein expression in human bladder cancer (BC) cells. Mechanistically, we observed that the RING domain stabilizes c-Myc by inhibiting its phosphorylation at Thr-58 and that this inhibition is due to activated ERK1/2-mediated phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser-9. Functional studies further revealed that c-Myc protein promotes anchorage-independent growth and invasion stimulated by the XIAP RING domain in human BC cells. Collectively, the findings in our study uncover that the RING domain of XIAP supports c-Myc protein stability, providing insight into the molecular mechanism and role of c-Myc overexpression in cance...Continue Reading

References

Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·X FangG B Mills
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·P Cohen, S Frame
Jul 18, 2002·The Journal of Biological Chemistry·Marion MacFarlaneGerald M Cohen
Oct 18, 2003·The Journal of Biological Chemistry·Mark A GregoryStephen R Hann
Jun 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Bruno Amati
Oct 12, 2007·The New England Journal of Medicine·John GearhartMegana K Prasad
Apr 27, 2012·Journal of the National Cancer Institute·Qing-Lian TangTiebang Kang
Jun 12, 2013·The EMBO Journal·Xing HuangMian Wu
Oct 5, 2013·OncoTargets and Therapy·Laurence DubrezValérie Glorian
Apr 23, 2014·Biochemical and Biophysical Research Communications·Wei GuoChuanshu Huang
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Jul 3, 2016·European Urology·Sebastien AntoniFreddie Bray
Jul 1, 2017·Cell Death & Disease·Arun MuraliKrishnaraj Rajalingam
Dec 19, 2017·International Journal of Cancer. Journal International Du Cancer·Yonghui YuChuanshu Huang
Dec 19, 2017·FEBS Letters·Bin WuZhenglun Zhu
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

❮ Previous
Next ❯

Citations

Jun 17, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Xiang AoYing Liu
Nov 4, 2020·Biomolecules·Huailu Tu, Max Costa
Apr 29, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Chong XueZipeng Cao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.