Ahsan, N and Shariq, M and Surolia, A and Raj, R and Khan, MF and Kumar, P (2024) Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins. In: Cellular and Molecular Biology Letters, 29 (1).
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Abstract
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: Figure not available: see fulltext. © 2024, The Author(s).
| Item Type: | Journal Article |
|---|---|
| Publication: | Cellular and Molecular Biology Letters |
| Publisher: | BioMed Central Ltd |
| Additional Information: | The copyright for this article belongs to author. |
| Keywords: | autophagy receptor; beclin 1; membrane receptor; mitogen activated protein kinase; protein p53; serine threonine protein kinase ULK1; signal peptide; tripartite motif protein; unclassified drug; apoptosis regulatory protein; tripartite motif protein, apoptosis; autophagosome; autophagy (cellular); bacterial pathogenesis; cancer therapy; cell fate; cell function; degenerative disease; degradation; human; immunomodulation; infection; lysophagy; malignant neoplasm; mitophagy; necroptosis; necrosis; nonhuman; pathogenesis; personalized medicine; protein function; regulatory mechanism; Review; ubiquitination; virus pathogenesis; chemistry; metabolism, Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Tripartite Motif Proteins; Ubiquitination |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 29 Feb 2024 11:34 |
| Last Modified: | 29 Feb 2024 11:34 |
| URI: | https://eprints.iisc.ac.in/id/eprint/83861 |
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