HMGB2 holds the key to the senescence-associated secretory phenotype
Open accessAbstract
The senescence-associated secretory phenotype (SASP) is a hallmark of senescence with an important physiological impact, but how it is established is unclear. In this issue, Aird et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201608026) describe how chromatin-bound HMGB2 fine tunes SASP expression by avoiding heterochromatin spreading.
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MacroH2A1, HMGB2, MLL1 and BRD4 regulate SASP factor gene expression in response to DNA damage.
“Other epigenetic regulators, such as macroH2A1, high mobility group box 2 (HMGB2), mixed‐lineage leukemia 1 (MLL1) and bromodomain‐containing protein 4 (BRD4), have been demonstrated as regulators of SASP factor gene expression in response to DNA damage.52, 53, 54, 55”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [53]
The paper’s Abstract reports that HMGB2 regulates SASP gene expression during oncogene-induced senescence. It links MLL1 to a DNA damage response, but does not establish that HMGB2 regulates SASP genes specifically in response to DNA damage. The cited paper therefore supports the HMGB2 portion of this multi-citation sentence, but not that condition for HMGB2. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOther epigenetic regulators such as BRD4, MLL1, HMGB2, macroH2A1, and GATA4 are involved in regulating SASP.
“Other epigenetic regulators such as BRD4 (Tasdemir et al., 2016), MLL1 (Capell et al., 2016), HMGB2 (Guerrero and Gil, 2016), histone variant macroH2A1 (Chen et al., 2015), and GATA4 (Kang et al., 2015) are also involved in regulating SASP.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Guerrero and Gil, 2016
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Cites
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“Remarkably, Aird et al. (2016) observed that the decrease in chromatin-bound HMGB2 correlated with reduced SASP gene expression but did not affect cell cycle arrest.”
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Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
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Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232 · see citing works
- Authors
- Guerrero, A., & Gil, J.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Guerrero, Ana
- Gil, Jesús
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2016-10-31
- Volume
- 215
- Issue
- 3
- Pages
- 297-299
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC5100298
- OpenAlex
- W2542373094
- Cited by
- 30
- References
- 15
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-sa)
- Funders
- Medical Research Council (MC-A652-5PZ00, MC_U120085810)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- HMGB2, senescence-associated secretory phenotype, cellular senescence, heterochromatin spreading, chromatin, gene expression regulation, heterochromatin
- MeSH terms
- Chromatin, Humans, Models, Biological, Phenotype, Down-Regulation, Cellular Senescence, HMGB2 Protein, Secretory Pathway, Cell Cycle Checkpoints
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