TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt

Hosseinalizadeh, Hamed; Mohamadzadeh, Omid; Kahrizi, Mohammad Saeed; Bahabadi, Zahra Razaghi; Klionsky, Daniel J.; Mirzei, Hamed

doi:10.1186/s11658-023-00418-z

Cited by 6 publications

(5 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Guardians Of Cell Fate: Trim Proteins and Their Regulation O...mentioning

confidence: 99%

“…It functions by triggering the phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit alpha (PIK3CA)/AKT1 signaling pathway and inhibits apoptosis and pyroptosis. TRIM8 also regulate NFKB and JAK-STAT pathways and can acts as a oncogene or tumor suppressor [171,172]. TRIM37 is associated with peroxisomal function and, together with peroxisomal biogenesis factor 5 (PEX5), regulates peroxisomal protein transport.…”

Section: Guardians Of Cell Fate: Trim Proteins and Their Regulation O...mentioning

confidence: 99%

See 1 more Smart Citation

Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins

Ahsan,

Shariq,

Surolia

et al. 2024

Cell Mol Biol Lett

View full text Add to dashboard Cite

TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases. Graphical Abstract

show abstract

Section: Guardians Of Cell Fate: Trim Proteins and Their Regulation O...mentioning

confidence: 99%

Section: Guardians Of Cell Fate: Trim Proteins and Their Regulation O...mentioning

confidence: 99%

Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins

Ahsan,

Shariq,

Surolia

et al. 2024

Cell Mol Biol Lett

View full text Add to dashboard Cite

show abstract

“…Furthermore, it should be noted that the suppressive impact of autophagy on MTORC1 is a contributing factor to the survival and stability of Treg cells. In Treg cells that are deficient in autophagy, the expression of MTORC1 is dysregulated, which in turn promotes the expression of c-Myc and glycolysis metabolic pathway ( 115 ). The stability impairment of autophagy-deficient Treg cells is partially restored by pharmacologically inhibiting MTORC1, MYC, or glycolytic activities ( 114 ).…”

Section: Treg-based Therapies In Cancermentioning

confidence: 99%

Regulating the regulatory T cells as cell therapies in autoimmunity and cancer

Hosseinalizadeh,

Rabiee,

Eghbalifard

et al. 2023

Front. Med.

Self Cite

View full text Add to dashboard Cite

Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.

show abstract

“…TRIM8 can also function as an oncogenic protein that leads to cell proliferation by cooperating with nuclear factor κB (NF-κB) and STAT3. 28 , 29 Furthermore, TRIM8-mediated stabilization of XIAP (X-linked Inhibitor of Apoptosis Protein), an important regulator of cell death and autophagy, prevents the activation of caspase-3 and resists apoptosis. 30 The function of TRIM8 may primarily depend on three pathways: the p53 oncogenic signaling pathway, the NF-κB pathway, and the JAK-STAT pathway, specifically STAT3 (signal transducer and activator of transcription 3) and its microenvironment.…”

Section: Introductionmentioning

confidence: 99%