Biology:Serotonylation

From HandWiki

Protein serotonylation refers to the post-translational modification in which the monoamine serotonin is covalently attached to glutamine residues on substrate proteins via transamidation. Serotonylation is a type of monoaminylation, which itself refers to the overall class of post-translational modifications involving monoamines. However, monoaminylation reactions are further classified by the individual monoamine reactant they describe (ie., serotonylation, dopaminylation, histaminylation).

Serotonylation has been reported for both histone and non-histone protein substrates, and thus represents a distinct neuroepigenetic and neuroproteomic regulatory mechanism with various implications in health and disease.[1] Since 2003, multiple studies have revealed the critical role of serotonylation in mediating a wide range of physiological processes, both in the nervous system and beyond.[1][2][3] Serotonylation is known to contribute to several significant diseases, including neuropsychiatric disorders such as depression and schizophrenia, as well as a variety of cancers.[1][4][5]

To date, notable protein serotonylation substrates include several metabolic enzymes (GAPDH, mTOR),[6][7] Rab GTPases (Rab3a, Rab27a),[8][9] Rho GTPases (RhoA, Rac1, Cdc42),[10][11][12] proteins involved in muscle contractility (⍺-actinin, SERCA2a),[13][14] extracellular matrix proteins (fibronectin),[15][16] neural surface proteins,[17] and Ras,[18] as well as the histone protein H3.[19][20][21]

Serotonylation has been reported in various cell types and tissues, including both serotonergic and dopaminergic neurons,[22][23] enterochromaffin cells,[24] cancer-associated fibroblasts,[25] pancreatic 𝛽-cells,[26] CD8+ T cells,[27] pulmonary endothelial cells,[28] platelets,[29] neutrophils,[21] mammary epithelial cells,[30] vascular smooth muscle,[31] and cells of the intestines.[18] Serotonylation is known to influence both tumorigenesis and cancer metastasis, and has been implicated in several types of cancer, including colorectal cancer,[7][32] neuroendocrine prostate cancer,[33] pancreatic cancer,[34] hepatocellular carcinoma,[35][36] and ependymomas (brain cancer).[37]

Identification

Protein monoaminylation was first discovered in 1957 by Heinrich Waelsch and colleagues at Columbia University. After demonstrating the incorporation of monoamines into proteins via transamidation at glutamine residues,[38] the group went on to uncover the enzyme catalyzing these reactions, effectively naming it "transglutaminase" after its function.[39][40]

Despite its discovery in the mid-twentieth century, protein monoaminylation was not investigated as a post-translational modification until 2003, when Diego Walther and colleagues at the Max-Planck-Institute for Molecular Genetics revealed that serotonylation of small GTPases mediates ⍺-granule release during the activation and aggregation of platelets.[29]

Notably, monoaminylation itself was not uncovered as an epigenetic regulatory mechanism until 2019, when Lorna Farrelly and colleagues at the Icahn School of Medicine reported the H3Q5-serotonylation (H3Q5ser) modification for the first time.[41] Thereafter, in 2021, Di Ye and colleagues at Sichuan University revealed mTOR-serotonylation as part of a novel feedback mechanism within the tryptophan pathway in colon cancer, demonstrating a link between protein serotonylation and cancer for the first time.[7]

Mechanism

Serotonylation is catalyzed by transglutaminase 2 (TGM2) in a calcium-dependent manner, and relies upon the intracellular bioavailability of serotonin substrates.[2][42] Generally, protein serotonylation occurs in the cytoplasm; however, histone serotonylation only occurs within the nucleus.[1][2] Nevertheless, the mechanism for TGM2-catalyzed serotonylation is identical for both histone and non-histone proteins alike.[1]

Structurally, Ca2+ binds directly to TGM2 itself and not to the substrate molecule.[42] Once Ca2+ binds to TGM2, a 4 nm relaxation about the major axis of the protein exposes the active site to available substrates.[42][43] The active site itself is composed of a well conserved catalytic triad (Cys277–His335–Asp358) situated within a substrate binding channel, which is bordered by two conserved residues (Trp241 and Trp332) that facilitate catalysis through stabilization of the transition state.[42][44] Once intracellular Ca2+ binds to TGM2 and exposes the substrate binding channel, the glutamine residue of a substrate protein (ie., histone H3, RhoA) is free to enter the enzyme active site.[1][42] As a transamidation reaction, the mechanism for protein serotonylation can be summarized in two parts: an initial thioester formation, followed by isopeptide bond formation.

Fig. 1 Mechanism for Protein Serotonylation
Serotonylation is a two step, Ca2+-dependent reaction in which TGM2 catalyzes the covalent attachment of a serotonin molecule onto the glutamine residue of a substrate protein. (A) The catalytic cysteine residue (Cys277) of TGM2 facilitates an initial acyl transfer reaction, which is ultimately followed by isopeptide bond formation (B). Common substrate proteins include Histone H3, small GTPases (RhoA, Rab3a), and extracellular matrix proteins (fibronectin).

When intracellular Ca2+ and serotonin concentrations are sufficient, TGM2-catalyzed serotonylation of substrate proteins can occur.[42] First, the catalytic cysteine residue (Cys277) in the TGM2 active site nucleophilically attacks the 𝛾-carboxamido group of the glutamine residue in an acyl transfer reaction (Fig. 1A), forming a thioester intermediate and releasing one molecule of ammonia (NH3) as a result.[1][42] Next, the deprotonated primary amine of the serotonin molecule nucleophilically attacks the 𝛾-thioester group of the intermediate, forming a stable isopeptide bond and ultimately releasing the enzyme (Fig. 1B).[1][42]

Function

Histone Serotonylation

With the discovery of histone monoaminylation in 2019, monoaminylation thus entered into the complex and ever-growing field of epigenetics, posing as a novel set of dynamic regulatory mechanisms.[1][18] To date, histone H3 is the only histone protein known to undergo monoaminylation modifications, and such modifications have only been reported for glutamine position 5 (Gln5) of histone H3 (hereafter referred to as H3Q5).[1] Thus, histone monoaminylation currently refers to the covalent addition of monoamines to glutamine at position 5 (Gln5) of histone H3.[1] Histone serotonylation remains the most widely reported histone monoaminylation modification to date, though both histone dopaminylation and histone histaminylation have also been reported.[1]

Histone monoaminylation modifications are associated with a number of regulatory effects, no two of which appear to be the same. H3Q5-serotonylation (H3Q5ser) has been reported in a wide range of tissues and cell types, including serotonergic neurons of the dorsal raphe nucleus,[19] astrocytes of the olfactory bulb,[45][46] the inferior alveolar nerve (ie., of the lip and lower jaw),[47] placenta,[48] ependymomas (brain cancers),[49] pancreatic ductal adenocarcinoma (PDAC) tissues,[50] cancer-associated fibroblasts,[25] hepatocellular carcinoma (HCC),[51][52] and neutrophils.[53] Combinatory effects between monoaminylation and other histone modifications have been reported.[19] Herein, low levels of trimethylation and serotonylation of histone H3 at lysine position 4 (H3K4) and glutamine position 5 (H3Q5), respectively (ie., H3K4me3Q5ser), in the dorsal raphe nucleus led to depressive symptoms in both male and female mice exposed to chronic stress.[19] Behavioral outcomes associated with H3K4me3Q5ser depletion were corrected by treatment with serotonin-associated antidepressants, thus evidencing such antidepressants as sufficient to attenuate stress-mediated gene expression and behavioral dysregulation.[19] Interestingly, corresponding patterns of H3K4me3Q5ser depletion were observed in the brains of major depressive disorder (MDD) patients on vs. off antidepressants at their time of death, thus evidencing a neurotransmission-independent role for serotonin in mediating both stress-associated and anti-depressant-associated transcriptional plasticity and behavioral outcomes.[19] Data as to the effects of H3Q5ser and H3K4me3Q5ser are displayed in detail within the table below:

Monoaminylation Tissue (or Cell) Type Modification Biological Function References
Serotonylation Dorsal Raphe Nucleus
(Serotonergic neurons)		 H3K4me3Q5ser High levels induce chronic stress-related gene expression programs and attenuate behavioral resilience to stressful stimuli (Al-Kachak et al., 2024)[42]
Serotonylation Olfactory bulb
(Astrocytes)		 H3Q5ser Regulates olfactory sensory processing by promoting astrocytic GABA release (Sardar et al., 2023)[54]
Serotonylation Inferior Alveolar Nerve
(ie., of the lip and lower jaw)		 H3Q5ser Promotes sensory neuron regeneration after inferior alveolar nerve transection, enhancing sensory recovery (Mao et al., 2025)[20]
Serotonylation Placenta H3Q5ser Significantly contributes to developmental gene expression programs in placenta, impacting key neurodevelopmental transcriptional networks in the offspring brain (Chan et al., 2024)[22]
Serotonylation Ependymomas
(Serotonergic neurons)		 H3Q5ser Promotes ependymoma tumorigenesis by dysregulating the expression of a core set of developmental transcription factors (Chen et al., 2024)[55]
Serotonylation Pancreatic Ductal Adenocarcinoma (PDAC) Tissues H3K4me3Q5ser Promotes pancreatic cancer progression by upregulating SCD and remodeling lipid metabolism (Lin et al., 2025)[51]
Serotonylation Cancer-associated fibroblasts (CAFs) H3Q5ser Enhances colorectal cancer (CRC) proliferation and invasiveness by triggering a pro-inflammatory phenotype in CAFs (Ling et al., 2024)[50]
Serotonylation Hepatocellular Carcinoma (HCC) H3Q5ser Promotes HCC tumor progression by increasing chromatin accessibility, leading to increased MYC transcriptional activity (Dong et al., 2025)[53]
Serotonylation Neutrophils H3Q5ser Induces the formation of neutrophil extracellular traps (NETs) in the liver, leading to metastases in neuroendocrine (NE) cancers (Liu et al., 2025)[25]
Serotonylation Rostral Ventrolateral Medulla (RVLM), Raphe Nuclei H3K4me3Q5ser Delays ejaculation by recruiting MZF1 to the DRD4 promoter, upregulating DRD4 expression (Gao et al., 2023)[56]

See Also

  • Monoaminylation
  • Histone Monoaminylation
  • Dopaminylation
  • Histaminylation

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Zhao, Yiqi; Zhang, Hongli; Yang, Yating; Chen, Wei-Dong; Wang, Yan-Dong (March 2026). "Monoaminylation in Human Health and Disease: State of the Field, Challenges, and Emerging Directions" (in en). Advanced Science 13 (16). doi:10.1002/advs.202520653. ISSN 2198-3844. PMID 41662496. Bibcode: 2026AdvSc..1320653Z. 
  2. ↑ 2.0 2.1 2.2 Walther, Diego J.; Stahlberg, Silke; Vowinckel, Jakob (December 2011). "Novel roles for biogenic monoamines: from monoamines in transglutaminase-mediated post-translational protein modification to monoaminylation deregulation diseases". The FEBS Journal 278 (24): 4740–4755. doi:10.1111/j.1742-4658.2011.08347.x. ISSN 1742-4658. PMID 21923757. 
  3. ↑ Penumatsa, K. C.; Fanburg, B. L. (2014-02-15). "Transglutaminase 2-mediated serotonylation in pulmonary hypertension". American Journal of Physiology. Lung Cellular and Molecular Physiology 306 (4): L309–315. doi:10.1152/ajplung.00321.2013. ISSN 1522-1504. PMID 24375797. 
  4. ↑ Chen, Yun-Zhou; Zhu, Xiu-Mei; Lv, Peng; Hou, Xi-Kai; Pan, Ying; Li, Ang; Du, Zhe; Xuan, Jin-Feng et al. (June 2024). "Association of histone modification with the development of schizophrenia". Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 175. doi:10.1016/j.biopha.2024.116747. ISSN 1950-6007. PMID 38744217. 
  5. ↑ Li, Huapeng; Wu, Jinghua; Zhang, Nan; Zheng, Qingfei (2024-08-28). "Transglutaminase 2-mediated histone monoaminylation and its role in cancer". Bioscience Reports 44 (8). doi:10.1042/BSR20240493. ISSN 1573-4935. PMID 39115570. 
  6. ↑ Wang, Xu; Fu, Sheng-Qiao; Yuan, Xiao; Yu, Feng; Ji, Qian; Tang, Hao-Wen; Li, Rong-Kun; Huang, Shan et al. (2024-02-15). "A GAPDH serotonylation system couples CD8+ T cell glycolytic metabolism to antitumor immunity". Molecular Cell 84 (4): 760–775.e7. doi:10.1016/j.molcel.2023.12.015. ISSN 1097-4164. PMID 38215751. 
  7. ↑ 7.0 7.1 7.2 Ye, Di; Xu, Huanji; Xia, Hongwei; Zhang, Chenliang; Tang, Qiulin; Bi, Feng (2021-05-18). "Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment". Journal of Experimental & Clinical Cancer Research: CR 40 (1): 173. doi:10.1186/s13046-021-01971-1. ISSN 1756-9966. PMID 34006301. 
  8. ↑ Paulmann, Nils; Grohmann, Maik; Voigt, Jörg-Peter; Bert, Bettina; Vowinckel, Jakob; Bader, Michael; Skelin, Masa; Jevsek, Marko et al. (October 2009). "Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation". PLOS Biology 7 (10). doi:10.1371/journal.pbio.1000229. ISSN 1545-7885. PMID 19859528. 
  9. ↑ Yoo, Yeong-Min; Joo, Seong Soo (2024-06-21). "Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells". International Journal of Molecular Sciences 25 (13): 6828. doi:10.3390/ijms25136828. ISSN 1422-0067. PMID 38999937. 
  10. ↑ Yu, Huangfei; Qu, Tianyin; Yang, Jinlan; Dai, Qing (2023-04-12). "Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression". Cell Communication and Signaling: CCS 21 (1): 75. doi:10.1186/s12964-023-01096-2. ISSN 1478-811X. PMID 37046308. 
  11. ↑ Sheftel, Celeste M.; Hernandez, Laura L. (2020). "Serotonin stimulated parathyroid hormone related protein induction in the mammary epithelia by transglutaminase-dependent serotonylation". PLOS ONE 15 (10). doi:10.1371/journal.pone.0241192. ISSN 1932-6203. PMID 33095824. Bibcode: 2020PLoSO..1541192S. 
  12. ↑ Mi, Zhen; Si, Tuda; Kapadia, Khushboo; Li, Qian; Muma, Nancy A. (2017-05-01). "Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines". Neuropharmacology 117: 93–105. doi:10.1016/j.neuropharm.2017.01.034. ISSN 1873-7064. PMID 28161375. 
  13. ↑ Watts, Stephanie W.; Priestley, Jessica R. C.; Thompson, Janice M. (2009-05-25). "Serotonylation of vascular proteins important to contraction". PLOS ONE 4 (5). doi:10.1371/journal.pone.0005682. ISSN 1932-6203. PMID 19479059. Bibcode: 2009PLoSO...4.5682W. 
  14. ↑ Wang, Qingjie; Wang, Dong; Yan, Gaoliang; Qiao, Yong; Sun, Ling; Zhu, Boqian; Wang, Xin; Tang, Chengchun (2016-11-18). "SERCA2a was serotonylated and may regulate sino-atrial node pacemaker activity". Biochemical and Biophysical Research Communications 480 (3): 492–497. doi:10.1016/j.bbrc.2016.10.082. ISSN 1090-2104. PMID 27780728. Bibcode: 2016BBRC..480..492W. 
  15. ↑ Hummerich, René; Schloss, Patrick (August 2010). "Serotonin--more than a neurotransmitter: transglutaminase-mediated serotonylation of C6 glioma cells and fibronectin". Neurochemistry International 57 (1): 67–75. doi:10.1016/j.neuint.2010.04.020. ISSN 1872-9754. PMID 20451572. 
  16. ↑ Hummerich, René; Thumfart, Jörg-Oliver; Findeisen, Peter; Bartsch, Dusan; Schloss, Patrick (2012-09-21). "Transglutaminase-mediated transamidation of serotonin, dopamine and noradrenaline to fibronectin: evidence for a general mechanism of monoaminylation". FEBS Letters 586 (19): 3421–3428. doi:10.1016/j.febslet.2012.07.062. ISSN 1873-3468. PMID 22858378. Bibcode: 2012FEBSL.586.3421H. 
  17. ↑ Hummerich, René; Schloss, Patrick (August 2010). "Serotonin--more than a neurotransmitter: transglutaminase-mediated serotonylation of C6 glioma cells and fibronectin". Neurochemistry International 57 (1): 67–75. doi:10.1016/j.neuint.2010.04.020. ISSN 1872-9754. PMID 20451572. 
  18. ↑ 18.0 18.1 18.2 Iida, Hiroki; Onuma, Takashi; Nakashima, Daiki; Mizutani, Daisuke; Hori, Takamitsu; Ueda, Kyohei; Hioki, Tomoyuki; Kim, Woo et al. (2023-01-13). "Tramadol regulates the activation of human platelets via Rac but not Rho/Rho-kinase" (in en). PLOS ONE 18 (1). doi:10.1371/journal.pone.0279011. ISSN 1932-6203. PMID 36638092. Bibcode: 2023PLoSO..1879011I. 
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 Al-Kachak, Amni; Di Salvo, Giuseppina; Fulton, Sasha L.; Chan, Jennifer C.; Farrelly, Lorna A.; Lepack, Ashley E.; Bastle, Ryan M.; Kong, Lingchun et al. (2024-06-13). "Histone serotonylation in dorsal raphe nucleus contributes to stress- and antidepressant-mediated gene expression and behavior" (in en). Nature Communications 15 (1): 5042. doi:10.1038/s41467-024-49336-4. ISSN 2041-1723. PMID 38871707. Bibcode: 2024NatCo..15.5042A. 
  20. ↑ 20.0 20.1 Chen, Hsiao-Chi; He, Peihao; McDonald, Malcolm; Williamson, Michael R.; Varadharajan, Srinidhi; Lozzi, Brittney; Woo, Junsung; Choi, Dong-Joo et al. (August 2024). "Histone serotonylation regulates ependymoma tumorigenesis" (in en). Nature 632 (8026): 903–910. doi:10.1038/s41586-024-07751-z. ISSN 1476-4687. PMID 39085609. Bibcode: 2024Natur.632..903C. 
  21. ↑ 21.0 21.1 Liu, Kaiyuan; Zhang, Yingchao; Du, Genyu; Chen, Xinyu; Xiao, Lingling; Jiang, Luyao; Jing, Na; Xu, Penghui et al. (2025-04-15). "5-HT orchestrates histone serotonylation and citrullination to drive neutrophil extracellular traps and liver metastasis". The Journal of Clinical Investigation 135 (8). doi:10.1172/JCI183544. ISSN 1558-8238. PMID 39903533. 
  22. ↑ 22.0 22.1 Gao, Pan; Liu, Xi; Zhu, Tianle; Gao, Rui; Gao, Jingjing; Zhang, Yao; Jiang, Hui; Huang, Houbao et al. (September 2023). "Vital function of DRD4 in dapoxetine medicated premature ejaculation treatment". Andrology 11 (6): 1175–1187. doi:10.1111/andr.13390. ISSN 2047-2927. PMID 36746766. 
  23. ↑ Penumatsa, K. C.; Fanburg, B. L. (2014-02-15). "Transglutaminase 2-mediated serotonylation in pulmonary hypertension". American Journal of Physiology. Lung Cellular and Molecular Physiology 306 (4): L309–315. doi:10.1152/ajplung.00321.2013. ISSN 1522-1504. PMID 24375797. 
  24. ↑ Ye, Di; Xu, Huanji; Xia, Hongwei; Zhang, Chenliang; Tang, Qiulin; Bi, Feng (2021-05-18). "Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment". Journal of Experimental & Clinical Cancer Research: CR 40 (1): 173. doi:10.1186/s13046-021-01971-1. ISSN 1756-9966. PMID 34006301. 
  25. ↑ 25.0 25.1 25.2 Ling, Tianlong; Dai, Zhanghan; Wang, Houming; Kien, Tran Trung; Cui, Rong; Yu, Tachung; Chen, Jianjun (2024-09-28). "Serotonylation in tumor-associated fibroblasts contributes to the tumor-promoting roles of serotonin in colorectal cancer". Cancer Letters 600. doi:10.1016/j.canlet.2024.217150. ISSN 0304-3835. PMID 39097134. https://www.sciencedirect.com/science/article/pii/S0304383524005457. 
  26. ↑ Yoo, Yeong-Min; Joo, Seong Soo (2024-06-21). "Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells". International Journal of Molecular Sciences 25 (13): 6828. doi:10.3390/ijms25136828. ISSN 1422-0067. PMID 38999937. 
  27. ↑ Wang, Xu; Fu, Sheng-Qiao; Yuan, Xiao; Yu, Feng; Ji, Qian; Tang, Hao-Wen; Li, Rong-Kun; Huang, Shan et al. (2024-02-15). "A GAPDH serotonylation system couples CD8+ T cell glycolytic metabolism to antitumor immunity". Molecular Cell 84 (4): 760–775.e7. doi:10.1016/j.molcel.2023.12.015. ISSN 1097-4164. PMID 38215751. 
  28. ↑ Guilluy, Christophe; Eddahibi, Saadia; Agard, Christian; Guignabert, Christophe; Izikki, Mohamed; Tu, Ly; Savale, Laurent; Humbert, Marc et al. (2009-06-15). "RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling". American Journal of Respiratory and Critical Care Medicine 179 (12): 1151–1158. doi:10.1164/rccm.200805-691OC. ISSN 1535-4970. PMID 19299501. 
  29. ↑ 29.0 29.1 Walther DJ, Peter JU, Winter S, Höltje M, Paulmann N, Grohmann M, Vowinckel J, Alamo-Bethencourt V, Wilhelm CS, Ahnert-Hilger G, Bader M. (2003). Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release. Cell. 115(7):851-62.doi:10.1016/S0092-8674(03)01014-6 PMID 14697203
  30. ↑ Sheftel, Celeste M.; Hernandez, Laura L. (2020). "Serotonin stimulated parathyroid hormone related protein induction in the mammary epithelia by transglutaminase-dependent serotonylation". PLOS ONE 15 (10). doi:10.1371/journal.pone.0241192. ISSN 1932-6203. PMID 33095824. Bibcode: 2020PLoSO..1541192S. 
  31. ↑ Watts, Stephanie W.; Priestley, Jessica R. C.; Thompson, Janice M. (2009-05-25). "Serotonylation of vascular proteins important to contraction". PLOS ONE 4 (5). doi:10.1371/journal.pone.0005682. ISSN 1932-6203. PMID 19479059. Bibcode: 2009PLoSO...4.5682W. 
  32. ↑ Yu, Huangfei; Qu, Tianyin; Yang, Jinlan; Dai, Qing (2023-04-12). "Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression" (in en). Cell Communication and Signaling 21 (1): 75. doi:10.1186/s12964-023-01096-2. ISSN 1478-811X. PMID 37046308. 
  33. ↑ Liu, Kaiyuan; Zhang, Yingchao; Du, Genyu; Chen, Xinyu; Xiao, Lingling; Jiang, Luyao; Jing, Na; Xu, Penghui et al. (2025-04-15). "5-HT orchestrates histone serotonylation and citrullination to drive neutrophil extracellular traps and liver metastasis". The Journal of Clinical Investigation 135 (8). doi:10.1172/JCI183544. ISSN 1558-8238. PMID 39903533. 
  34. ↑ Lin, Sang; Tan, Sheng; Peng, Yonglin; Tulamaiti, Aziguli; Du, Wenfei; Ding, Keshuo; Chen, Changyu; Wu, Jun et al. (2025-07-01). "Histone serotonylation promotes pancreatic cancer development via lipid metabolism remodeling" (in en). Nature Communications 16 (1): 5947. doi:10.1038/s41467-025-61197-z. ISSN 2041-1723. PMID 40593695. Bibcode: 2025NatCo..16.5947L. 
  35. ↑ Navarro-Corcuera, Amaia; Martínez-Chantar, María L. (July 2025). "Histone serotonylation in HCC: Decoding the impact of "happy" histones on liver cancer progression". Journal of Hepatology 83 (1): 18–20. doi:10.1016/j.jhep.2025.02.020. ISSN 1600-0641. PMID 40023196. 
  36. ↑ Dong, Renshun; Wang, Tianci; Dong, Wei; Zhang, Haoquan; Li, Yani; Tao, Ran; Liu, Qiumeng; Liang, Huifang et al. (July 2025). "TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway". Journal of Hepatology 83 (1): 105–118. doi:10.1016/j.jhep.2024.12.038. ISSN 1600-0641. PMID 39788430. 
  37. ↑ Chen, Hsiao-Chi; He, Peihao; McDonald, Malcolm; Williamson, Michael R.; Varadharajan, Srinidhi; Lozzi, Brittney; Woo, Junsung; Choi, Dong-Joo et al. (August 2024). "Histone serotonylation regulates ependymoma tumorigenesis" (in en). Nature 632 (8026): 903–910. doi:10.1038/s41586-024-07751-z. ISSN 1476-4687. PMID 39085609. Bibcode: 2024Natur.632..903C. 
  38. ↑ Sarkar, Nirmal K.; Clarke, Donald D.; Waelsch, Heinrich (1957-01-01). "An enzymically catalyzed incorporation of amines into proteins". Biochimica et Biophysica Acta 25 (2): 451–452. doi:10.1016/0006-3002(57)90512-7. ISSN 0006-3002. PMID 13471608. 
  39. ↑ Mycek, M. J.; Clarke, D. D.; Neidle, A.; Waelsch, H. (1959-10-01). "Amine incorporation into insulin as catalyzed by transglutaminase". Archives of Biochemistry and Biophysics 84 (2): 528–540. doi:10.1016/0003-9861(59)90613-7. ISSN 0003-9861. PMID 14425580. 
  40. ↑ Bader, Michael (2019-11-21). "Serotonylation: Serotonin Signaling and Epigenetics" (in English). Frontiers in Molecular Neuroscience 12. doi:10.3389/fnmol.2019.00288. ISSN 1662-5099. PMID 31824263. 
  41. ↑ Farrelly, Lorna A.; Thompson, Robert E.; Zhao, Shuai; Lepack, Ashley E.; Lyu, Yang; Bhanu, Natarajan V.; Zhang, Baichao; Loh, Yong-Hwee E. et al. (March 2019). "Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3" (in en). Nature 567 (7749): 535–539. doi:10.1038/s41586-019-1024-7. ISSN 1476-4687. PMID 30867594. Bibcode: 2019Natur.567..535F. 
  42. ↑ 42.0 42.1 42.2 42.3 42.4 42.5 42.6 42.7 42.8 Király, Róbert; Demény, MátéÁ.; Fésüs, László (2011). "Protein transamidation by transglutaminase 2 in cells: a disputed Ca2+-dependent action of a multifunctional protein" (in en). The FEBS Journal 278 (24): 4717–4739. doi:10.1111/j.1742-4658.2011.08345.x. ISSN 1742-4658. PMID 21902809. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1742-4658.2011.08345.x. 
  43. ↑ Di Venere, A.; Rossi, A.; De Matteis, F.; Rosato, N.; Agrò, A. F.; Mei, G. (2000-02-11). "Opposite effects of Ca(2+) and GTP binding on tissue transglutaminase tertiary structure". The Journal of Biological Chemistry 275 (6): 3915–3921. doi:10.1074/jbc.275.6.3915. ISSN 0021-9258. PMID 10660544. 
  44. ↑ Iismaa, Siiri E.; Holman, Sara; Wouters, Merridee A.; Lorand, Laszlo; Graham, Robert M.; Husain, Ahsan (2003-10-28). "Evolutionary specialization of a tryptophan indole group for transition-state stabilization by eukaryotic transglutaminases". Proceedings of the National Academy of Sciences of the United States of America 100 (22): 12636–12641. doi:10.1073/pnas.1635052100. ISSN 0027-8424. PMID 14566064. Bibcode: 2003PNAS..10012636I. 
  45. ↑ Sardar, Debosmita; Cheng, Yi-Ting; Woo, Junsung; Choi, Dong-Joo; Lee, Zhung-Fu; Kwon, Wookbong; Chen, Hsiao-Chi; Lozzi, Brittney et al. (2023-06-16). "Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation". Science (New York, N.Y.) 380 (6650). doi:10.1126/science.ade0027. ISSN 1095-9203. PMID 37319217. 
  46. ↑ Sardar, Debosmita; Cheng, Yi-Ting; Woo, Junsung; Choi, Dong-Joo; Lee, Zhung-Fu; Kwon, Wookbong; Chen, Hsiao-Chi; Lozzi, Brittney; Cervantes, Alexis; Rajendran, Kavitha; Huang, Teng-Wei; Jain, Antrix; Arenkiel, Benjamin; Maze, Ian; Deneen, Benjamin (2023-02-27). "Activity-dependent induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation". pp. 2023.02.24.529904. bioRxiv 10.1101/2023.02.24.529904.
  47. ↑ Mao, Suning; Zhang, Gaowei; Ma, Pingchuan; Ma, Zhongkai; Li, Chunjie; Ye, Li (2025-10-01). "Serotonin promotes lip sensory recovery after inferior alveolar nerve transection via histone serotonylation". Journal of Dental Sciences 20 (4): 2363–2374. doi:10.1016/j.jds.2025.04.001. ISSN 1991-7902. PMID 41040553. 
  48. ↑ Chan, Jennifer C.; Alenina, Natalia; Cunningham, Ashley M.; Ramakrishnan, Aarthi; Shen, Li; Bader, Michael; Maze, Ian (2024-04-01). "Serotonin Transporter-dependent Histone Serotonylation in Placenta Contributes to the Neurodevelopmental Transcriptome". Journal of Molecular Biology. Interpreting Combinatorial Epigenetic Modifications for Biological Meaning 436 (7). doi:10.1016/j.jmb.2024.168454. ISSN 0022-2836. PMID 38266980. 
  49. ↑ Chen, Hsiao-Chi; He, Peihao; McDonald, Malcolm; Williamson, Michael R.; Varadharajan, Srinidhi; Lozzi, Brittney; Woo, Junsung; Choi, Dong-Joo et al. (August 2024). "Histone serotonylation regulates ependymoma tumorigenesis" (in en). Nature 632 (8026): 903–910. doi:10.1038/s41586-024-07751-z. ISSN 1476-4687. PMID 39085609. Bibcode: 2024Natur.632..903C. 
  50. ↑ 50.0 50.1 Lin, Sang; Tan, Sheng; Peng, Yonglin; Tulamaiti, Aziguli; Du, Wenfei; Ding, Keshuo; Chen, Changyu; Wu, Jun et al. (2025-07-01). "Histone serotonylation promotes pancreatic cancer development via lipid metabolism remodeling" (in en). Nature Communications 16 (1): 5947. doi:10.1038/s41467-025-61197-z. ISSN 2041-1723. PMID 40593695. Bibcode: 2025NatCo..16.5947L. 
  51. ↑ 51.0 51.1 Navarro-Corcuera, Amaia; Martínez-Chantar, María L. (July 2025). "Histone serotonylation in HCC: Decoding the impact of "happy" histones on liver cancer progression". Journal of Hepatology 83 (1): 18–20. doi:10.1016/j.jhep.2025.02.020. ISSN 0168-8278. PMID 40023196. https://linkinghub.elsevier.com/retrieve/pii/S0168827825001291. 
  52. ↑ Dong, Renshun; Wang, Tianci; Dong, Wei; Zhang, Haoquan; Li, Yani; Tao, Ran; Liu, Qiumeng; Liang, Huifang et al. (July 2025). "TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway". Journal of Hepatology 83 (1): 105–118. doi:10.1016/j.jhep.2024.12.038. ISSN 0168-8278. PMID 39788430. https://linkinghub.elsevier.com/retrieve/pii/S0168827824028290. 
  53. ↑ 53.0 53.1 Liu, Kaiyuan; Zhang, Yingchao; Du, Genyu; Chen, Xinyu; Xiao, Lingling; Jiang, Luyao; Jing, Na; Xu, Penghui et al. (2025-04-15). "5-HT orchestrates histone serotonylation and citrullination to drive neutrophil extracellular traps and liver metastasis" (in en). Journal of Clinical Investigation 135 (8). doi:10.1172/JCI183544. ISSN 1558-8238. PMID 39903533. 
  54. ↑ Rajan, Koilmani Emmanuvel; Karen, Christopher; Dhivakar, Selvavinayagam (2023-07-13). "Early-life stressful social experience (SSE) alters ultrasound vocalizations and impairs novel odor preference: Influence of histone dopaminylation". Neuroscience Letters 809. doi:10.1016/j.neulet.2023.137304. ISSN 0304-3940. https://www.sciencedirect.com/science/article/pii/S030439402300263X. 
  55. ↑ "Serotonin pharmacology in the gastrointestinal tract: a review". Naunyn-Schmiedeberg's Archives of Pharmacology 377 (3): 181–203. May 2008. doi:10.1007/s00210-008-0276-9. PMID 18398601. 
  56. ↑ Gao, Pan; Liu, Xi; Zhu, Tianle; Gao, Rui; Gao, Jingjing; Zhang, Yao; Jiang, Hui; Huang, Houbao et al. (September 2023). "Vital function of DRD4 in dapoxetine medicated premature ejaculation treatment" (in en). Andrology 11 (6): 1175–1187. doi:10.1111/andr.13390. ISSN 2047-2919. PMID 36746766. https://onlinelibrary.wiley.com/doi/10.1111/andr.13390. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Serotonylation&oldid=4433499"