Les protéines de la famille TSC-22D

Pépin, Aurélie; Biola-Vidamment, Armelle; Laté, Perle Latré de; Espinasse, Marie-Alix; Godot, Véronique; Pallardy, Marc

doi:10.1051/medsci/20153101016

Cited by 4 publications

(4 citation statements)

References 39 publications

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“…Little is known about TSC22D2 except for its possible suppressive role in colorectal tumorigenesis 67 . Although TSC22D genes may have distinct roles in specific tissues or cell types, we find the protein sequence features and expression patterns 63 shared by the TSC22D gene products (at least for TSC22D1, TSC22D2, and TSC22D4) show striking similarities and behave like cytoplasmic crowding sensors. Our work demonstrates that the TSC22D gene family is a stark example of evolution creating redundancy amongst the TSC22D proteins to allow intermingling with NRBPs and WNKs for cytoplasmic crowd sensing and cell volume regulation.…”

Section: Discussionmentioning

confidence: 83%

“…However, no direct evidence has been reported for the transcription regulation activity of TSC22D family proteins under physiological conditions. While TSC22D1 (TSC-22) and TSC22D3 (GILZ) are the most studied of the TSC22D proteins (reviewed by Pépin et al 63 ), more recent studies have demonstrated a role for TSC22D4 in liver metabolism and hepatic metabolic dysfunction in liver cancer models [64][65][66] . Little is known about TSC22D2 except for its possible suppressive role in colorectal tumorigenesis 67 .…”

Section: Discussionmentioning

confidence: 99%

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TSC22D,WNKandNRBPgene families exhibit functional buffering and evolved with Metazoa for macromolecular crowd sensing

Xiao,

Lee,

Aguilera-Uribe

et al. 2024

Preprint

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The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. Myriad redundancies have evolved across all facets of osmosensing in metazoans, including among water and ion transporters, regulators of cellular morphology, and macromolecular crowding sensors, hampering efforts to gain a clear understanding of how cells respond to rapid water loss. In this study, we harness the power of gene co-essentiality analysis and genome-scale CRISPR-Cas9 screening to identify an unappreciated relationship between TSC22D2, WNK1 and NRBP1 in regulating cell volume homeostasis. Each of these genes have paralogs and are functionally buffered for macromolecular crowd sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK and NRBP family members physically associate into cytoplasmic biocondensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans reveals that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is concomitant with rapid IDR length expansion in WNK family kinases. Our study identifies functions for unrecognized components of the cell volume sensing machinery and reveals that TSC22D, WNK and NRBP genes evolved as cytoplasmic crowding sensors in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

TSC22D,WNKandNRBPgene families exhibit functional buffering and evolved with Metazoa for macromolecular crowd sensing

Xiao,

Lee,

Aguilera-Uribe

et al. 2024

Preprint

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“…TSC-22 is part of a family in which many mRNAs with different lengths are transcribed from four different genes as splice variants, and many proteins are translated from these mRNAs [15,16]. The proteins reported to date are shown in Table 1 [8][9][10][11][12][13][14][16][17][18][19][20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…Kester et al found that only leucine residues at positions 91 and 97 of the LZ domain are essential for TSC-22 family proteins (THG1) to form a homo-or heterodimer [24]. In addition, some TSC-22 proteins may interact with proteins that are not in the TSC-22 family or have no LZ [15]. However, regulatory factors upstream of TSC22D1 family proteins and downstream of intracellular signaling molecules that might bind to TSC22D1 family proteins have yet to be identified.…”

Section: Introductionmentioning

confidence: 99%

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

Kamimura

Uchida

Kanno

et al. 2021

IJMS

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TSC-22 (TGF-β stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

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Les cellules dendritiques humaines dans l’asthme et la rhinite allergique

Froidure

Pilette

2015

Med Sci (Paris)

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Les protéines de la famille TSC-22D

Cited by 4 publications

References 39 publications

TSC22D,WNKandNRBPgene families exhibit functional buffering and evolved with Metazoa for macromolecular crowd sensing

TSC22D,WNKandNRBPgene families exhibit functional buffering and evolved with Metazoa for macromolecular crowd sensing

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

Les cellules dendritiques humaines dans l’asthme et la rhinite allergique

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