The Multiple Roles of the IAP Super-family in cancer

Kumar, Seeram Satish; Fairmichael, Ciaran; Longley, Daniel B.; Turkington, Richard

doi:10.1016/j.pharmthera.2020.107610

Cited by 39 publications

(22 citation statements)

References 238 publications

(208 reference statements)

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“…E3 ubiquitin ligase can maintain protein balance and cell homeostasis by mediating the ubiquitination modification of functional proteins. Once the ubiquitination regulation of key proteins is abnormal, cells with persistent imbalance in homeostasis may become cancerous 46 , 47 . As one of the more active E3 ubiquitin ligases, Smurf1 has been reported to be involved in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma

Cui

Yan

et al. 2022

npj Precis. Onc.

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Long non-coding RNAs (LncRNAs) play important roles in the development of human esophageal squamous cell carcinoma (ESCC). Our previous studies have shown that knockdown of LncRNA ESCCAL-1 expression inhibits the growth of ESCC cells, but the mechanisms remain largely unknown. In this study, we show that over-expression of ESCCAL-1 promotes ESCC cell proliferation and cell-cycle progression by blocking ubiquitin-mediated degradation of an oncoprotein galectin-1 (Gal-1). Multiple LncRNA expression datasets as well as our own data together reveal that ESCCAL-1 is evidently up-regulated in ESCC tissues and exhibits promising diagnostic value. Over-expression of ESCCAL-1 augmented ESCC cell proliferation and cell-cycle progression, whereas down-regulation of ESCCAL-1 resulted in the opposite effects. Mechanistically, LncRNA ESCCAL-1 directly binds to Gal-1 and positively regulates its protein level without affecting its mRNA level. Up-regulation of Gal-1 facilitated ESCC cell proliferation and cell-cycle progress. Knockdown of Gal-1 mitigated the effects of ESCCAL-1-mediated high cellular proliferation, NF-κB signaling activation and tumorigenicity of ESCC cells. Thus, our findings provide novel insight into the mechanism by which ESCCAL-1 facilitates ESCC tumorigenesis and cell-cycle progression by interacting with and stabilizing Gal-1 protein, suggesting a potential therapeutic target for ESCC.

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Section: Discussionmentioning

confidence: 99%

ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma

Cui

Yan

et al. 2022

npj Precis. Onc.

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“…Clearly, a fluorescence approach or CD measurements will be needed to expand the scope of our findings to confirm the binding of Ln ions to cIAP2. Given that IAPs are regarded as therapeutic targets [ 41 ], their structures have been extensively studied. Unfortunately, all the reported constructs used for structural analysis of cIAP2 are limited to BIR and RING domains and thus are deprived of LBTs [ 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase SPL2 Is a Lanthanide-Binding Protein

Tracz

Górniak

Szczepaniak

et al. 2021

IJMS

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The SPL2 protein is an E3 ubiquitin ligase of unknown function. It is one of only three types of E3 ligases found in the outer membrane of plant chloroplasts. In this study, we show that the cytosolic fragment of SPL2 binds lanthanide ions, as evidenced by fluorescence measurements and circular dichroism spectroscopy. We also report that SPL2 undergoes conformational changes upon binding of both Ca2+ and La3+, as evidenced by its partial unfolding. However, these structural rearrangements do not interfere with SPL2 enzymatic activity, as the protein retains its ability to auto-ubiquitinate in vitro. The possible applications of lanthanide-based probes to identify protein interactions in vivo are also discussed. Taken together, the results of this study reveal that the SPL2 protein contains a lanthanide-binding site, showing for the first time that at least some E3 ubiquitin ligases are also capable of binding lanthanide ions.

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“…Chez les mammifères, la famille des IAP compte huit membres : cIAP1, cIAP2 (cellular IAP1 et IAP2), XIAP (X-linked IAP), NAIP (neural apoptosis inhibitory protein), Apollon, Livin, ILP2 (IAP-like protein 2) et la survivine. De nombreuses études ont démontré leurs rôles dans des processus cellulaires variés, comme la réponse inflammatoire, la différenciation, la prolifération , la réponse immu-nitaire innée et la motilité des cellules [1]. Il a également été montré que certaines de ces protéines IAP, comme les protéines cIAP1 et cIAP2, étaient capables de se lier aux caspases sans les inhiber [2].…”

Section: Les Protéines Inhibitrices De L'apoptose De La Famille Iapunclassified

IAP et cancer : le NO contre-attaque

2021

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Dans le cadre du Master 2 de l’université EPHE-PSL (Master Sciences du vivant, cursus IMaGHE, parcours Physiopathologie intégrative [PPI]), des étudiants se sont confrontés à la rédaction d’une nouvelle scientifique. Ces étudiants ayant choisi une spécialisation en cancérologie, l’équipe pédagogique leur a proposé de faire une synthèse d’articles sur deux thématiques : 1) les protéines IAP et un mécanisme original de régulation de leur activité par S-nitrosylation et 2) la séparase, dont un article paru récemment dans Nature montre qu’elle jouerait un rôle inattendu dans la protection des cellules contre la transformation tumorale. Organisés en binôme ou trinôme, les étudiants ont rédigé deux nouvelles qui soulignent l’intérêt des travaux analysés, ainsi que leur originalité. Ils se sont pleinement investis dans cette tâche et ont su faire preuve d’un bel esprit de synthèse. Ils ont apprécié cet exercice nouveau pour eux, mais qui leur a permis d’avoir un aperçu de la publication scientifique inhérente au métier de chercheur auquel ils se destinent.

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The Multiple Roles of the IAP Super-family in cancer

Cited by 39 publications

References 238 publications

ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma

ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma

E3 Ubiquitin Ligase SPL2 Is a Lanthanide-Binding Protein

IAP et cancer : le NO contre-attaque

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