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Role of TSC1 in physiology and diseases

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Abstract

Since its initial discovery as the gene altered in Tuberous Sclerosis Complex (TSC), an autosomal dominant disorder, the interest in TSC1 (Tuberous Sclerosis Complex 1) has steadily risen. TSC1, an essential component of the pro-survival PI3K/AKT/MTOR signaling pathway, plays an important role in processes like development, cell growth and proliferation, survival, autophagy and cilia development by co-operating with a variety of regulatory molecules. Recent studies have emphasized the tumor suppressive role of TSC1 in several human cancers including liver, lung, bladder, breast, ovarian, and pancreatic cancers. TSC1 perceives inputs from various signaling pathways, including TNF-α/IKK-β, TGF-β-Smad2/3, AKT/Foxo/Bim, Wnt/β-catenin/Notch, and MTOR/Mdm2/p53 axis, thereby regulating cancer cell proliferation, metabolism, migration, invasion, and immune regulation. This review provides a first comprehensive evaluation of TSC1 and illuminates its diverse functions apart from its involvement in TSC genetic disorder. Further, we have summarized the physiological functions of TSC1 in various cellular events and conditions whose dysregulation may lead to several pathological manifestations including cancer.

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Funding

This work was financially supported by the Department of Biotechnology, New Delhi (Grant# BT/PR10272/BRB/10/1266/2013) to AK and a junior research fellowship from DBT to KM. We also thank DST-FIST [SR/FST/LS11-036/2014(C)] and UGC-SAP [F.4.13/2018/DRS-III (SAP-II)] for financial support.

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  1. Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India

    Karthik Mallela & Arun Kumar

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  1. Karthik Mallela
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KM wrote the first draft of the manuscript, and AK supervised the manuscript writing. Both the authors have read and agreed to the published version of the manuscript.

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Correspondence to Arun Kumar.

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Mallela, K., Kumar, A. Role of TSC1 in physiology and diseases. Mol Cell Biochem 476, 2269–2282 (2021). https://doi.org/10.1007/s11010-021-04088-3

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