FADD phosphorylation impaired islet morphology and function

Yao, Chun; Zhuang, Hongqin; Cheng, Wei; Lin, Yan; Du, Pan; Yang, Bo; Huang, Xiaofeng; Chen, Sheng; Hu, Qingang; Hua, Zichun

doi:10.1002/jcp.24885

Cited by 4 publications

(3 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several phosphorylation sites have been identified in FADD [89,90,91], but the most relevant site conserved between mice and humans is serine 191 and serine 194, respectively [90]. The impact of FADD phosphorylation on apoptosis is controversial [5,90,92,93]. Our data indicate that the phosphorylation status of FADD does not affect apoptosis [13], but FADD phosphorylation could affect apoptosis indirectly, as a consequence of protein availability in the cell.…”

Section: Posttranslational Modifications Of Fadd Proteinmentioning

confidence: 99%

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Marín-Rubio

Vela‐Martín

Fernández‐Piqueras

et al. 2019

Cancers

View full text Add to dashboard Cite

FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value.

show abstract

Section: Posttranslational Modifications Of Fadd Proteinmentioning

confidence: 99%

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Marín-Rubio

Vela‐Martín

Fernández‐Piqueras

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…In the mouse model of FADD-D (S191D), which mimics the constitutive expression of phosphorylated FADD in mice, the area of pancreatic islets is shrunken, and GSIS is impaired. This suggests that FADD phosphorylation negatively regulates islet development and insulin secretion (Yao et al, 2015).…”

Section: Phosphorylationmentioning

confidence: 98%

Regulation of insulin secretion by the post-translational modifications

Yang

Wei

Zhao

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic β cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in β cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in β cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.

show abstract

“…Fas-associated death domain-containing protein (FADD) is known to regulate insulin secretion and islet development [ 87 ]. FADD phosphorylation has been suggested to be involved in insulin degradation, as evidenced by the compromised insulin production and increased insulin levels in serum of FADD-D (FADD phosphorylation-mimic mutation) mice [ 87 ]. A recent study demonstrated that FADD phosphorylation downregulates the mRNA and protein levels of insulin-degrading enzymes (IDEs) [ 52 ].…”

Section: Ptms In Type 2 Diabetesmentioning

confidence: 99%

Post-Translational Modifications and Diabetes

Sharma,

Hamza,

Boyle

et al. 2024

Biomolecules

View full text Add to dashboard Cite

Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention. Accumulative evidence suggests that protein post-translational modifications (PTMs), including glycosylation, phosphorylation, acetylation, and SUMOylation, play important roles in diabetes and its pathological consequences. Therefore, the investigation of these PTMs not only sheds important light on the mechanistic regulation of diabetes but also opens new avenues for targeted therapies. Here, we offer a comprehensive overview of the role of several PTMs in diabetes, focusing on the most recent advances in understanding their functions and regulatory mechanisms. Additionally, we summarize the pharmacological interventions targeting PTMs that have advanced into clinical trials for the treatment of diabetes. Current challenges and future perspectives are also provided.

show abstract

FADD phosphorylation impaired islet morphology and function

Cited by 4 publications

References 53 publications

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Regulation of insulin secretion by the post-translational modifications

Post-Translational Modifications and Diabetes

Contact Info

Product

Resources

About