CRL2APPBP2-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

Huang, Daoyuan; Zhao, Qian; Yang, Kuan; Lei, Jinghui; Jing, Ying; Li, Hongyu; Zhang, Chen; Ma, Shuai; Sun, Shuhui; Cai, Yusheng; Wang, Guibin; Qu, Jing; Zhang, Weiqi; Wang, Si; Liu, Guang-Hui

doi:10.1007/s11427-023-2451-3

Cited by 6 publications

(1 citation statement)

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“…3A ; Table S7 ). The iCAS-DNAmAge comprises 65 CpG sites, with 35 being upregulated with age and associated with protein ubiquitination, a pathway closely related to protein homeostasis that is critical in the aging process ( Huang et al, 2023 ; Zhang et al, 2022 ), while the remaining 30 are downregulated with aging and linked to protein phosphorylation ( Fig. 3D and 3E ).…”

Section: Resultsmentioning

confidence: 99%

DNA methylation clocks for estimating biological age in Chinese cohorts

Zheng,

Li,

Liu

et al. 2024

Protein &Amp; Cell

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Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation at specific CpG sites. However, available DNA methylation (DNAm) age predictors are based on datasets with limited ethnic representation. Moreover, a systematic comparison between DNAm data and other omics datasets has not yet been performed. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation (DNAm) aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing basis for evaluating aging intervention strategies.

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Section: Resultsmentioning

confidence: 99%

DNA methylation clocks for estimating biological age in Chinese cohorts

Zheng,

Li,

Liu

et al. 2024

Protein &Amp; Cell

Self Cite

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TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2

Tan,

Miao,

Luo

et al. 2024

Advanced Science

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Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis‐Specific Protein, Y‐Encoded‐Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFβ signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial‐mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFβ signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFβ to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter‐balancing role of TSPYL1 and TSPYL2 in regulating TGFβ signaling is also unraveled.

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