Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review)

Qian, Jinjun; Yang, Ye; Gu, Chunyan

doi:10.3892/ijo.2021.5253

Cited by 7 publications

(3 citation statements)

References 205 publications

(233 reference statements)

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“…SUMOylation has emerged as a host key signaling pathway that has a diverse role in host-mediated immune responses for many viral diseases and cancer biology ( Wang et al., 2013 ; Saul et al., 2015 ; Xia et al., 2015 ; Xu et al., 2015 ; Liu et al., 2016 ; Wang et al., 2021 ). To establish the infection and sustain its survival, Leishmania parasites successfully manage to evade the host immune mechanism, but information on the host factors or signaling pathways that are modulated by the parasite for the stable infection has not been analyzed in detail.…”

Section: Discussionmentioning

confidence: 99%

Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival

Singhal

Madan

Chaurasiya

et al. 2022

Front. Cell. Infect. Microbiol.

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SUMOylation is one of the post-translational modifications that have recently been described as a key regulator of various cellular, nuclear, metabolic, and immunological processes. The process of SUMOylation involves the modification of one or more lysine residues of target proteins by conjugation of a ubiquitin-like, small polypeptide known as SUMO for their degradation, stability, transcriptional regulation, cellular localization, and transport. Herein, for the first time, we report the involvement of the host SUMOylation pathway in the process of infection of Leishmania donovani, a causative agent of visceral leishmaniasis. Our data revealed that infection of L. donovani to the host macrophages leads to upregulation of SUMOylation pathway genes and downregulation of a deSUMOylating gene, SENP1. Further, to confirm the effect of the host SUMOylation on the growth of Leishmania, the genes associated with the SUMOylation pathway were silenced and parasite load was analyzed. The knockdown of the SUMOylation pathway led to a reduction in parasitic load, suggesting the role of the host SUMOylation pathway in the disease progression and parasite survival. Owing to the effect of the SUMOylation pathway in autophagy, we further investigated the status of host autophagy to gain mechanistic insights into how SUMOylation mediates the regulation of growth of L. donovani. Knockdown of genes of host SUMOylation pathway led to the reduction of the expression levels of host autophagy markers while promoting autophagosome–lysosome fusion, suggesting SUMOylation-mediated autophagy in terms of autophagy initiation and autophagy maturation during parasite survival. The levels of reactive oxygen species (ROS) generation, nitric oxide (NO) production, and pro-inflammatory cytokines were also elevated upon the knockdown of genes of the host SUMOylation pathway during L. donovani infection. This indicates the involvement of the SUMOylation pathway in the modulation of protective immune responses and thus favoring parasite survival. Taken together, the results of this study indicate the hijacking of the host SUMOylation pathway by L. donovani toward the suppression of host immune responses and facilitation of host autophagy to potentially facilitate its survival. Targeting of SUMOylation pathway can provide a starting point for the design and development of novel therapeutic interventions to combat leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival

Singhal

Madan

Chaurasiya

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Sumoylation is another important protein PTM discovered more than two decades ago, which involves the covalent addition of small ubiquitin‐like modifier (SUMO) protein (around 12 kDa) through its C‐terminus to lysine residues of a target substrate (Celen & Sahin, 2020; Wang et al , 2021). So far, five SUMO isoforms have been identified in mammals, of which SUMO 1–3 have been well studied for their roles in stress response and cellular physiology (Zhao, 2018), whereas little is known about SUMO 4–5 (Baczyk et al , 2017; Li et al , 2017).…”

Section: Introductionmentioning

confidence: 99%

Oxygen‐regulated post‐translation modifications as master signalling pathway in cells

Batie,

Fasanya,

Kenneth

et al. 2023

EMBO Reports

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Oxygen is essential for viability in mammalian organisms. However, cells are often exposed to changes in oxygen availability, due to either increased demand or reduced oxygen supply, herein called hypoxia. To be able to survive and/or adapt to hypoxia, cells activate a variety of signalling cascades resulting in changes to chromatin, gene expression, metabolism and viability. Cellular signalling is often mediated via post‐translational modifications (PTMs), and this is no different in response to hypoxia. Many enzymes require oxygen for their activity and oxygen can directly influence several PTMS. Here, we review the direct impact of changes in oxygen availability on PTMs such as proline, asparagine, histidine and lysine hydroxylation, lysine and arginine methylation and cysteine dioxygenation, with a focus on mammalian systems. In addition, indirect hypoxia‐dependent effects on phosphorylation, ubiquitination and sumoylation will also be discussed. Direct and indirect oxygen‐regulated changes to PTMs are coordinated to achieve the cell's ultimate response to hypoxia. However, specific oxygen sensitivity and the functional relevance of some of the identified PTMs still require significant research.

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“…The SUMO field continues to expand at a rapid pace, with over 180 studies in the past year alone demonstrating the role of SUMOylation in human pathophysiological conditions. For example, targeting SUMOylation may have clinical implications for cancer treatment ( Ma et al, 2021 ), including prostate cancer ( Wang and Yu, 2021 ), colorectal cancer ( Peng et al, 2021 ), hematological malignancies ( Wang et al, 2021a ), bone chondrosarcoma ( Kroonen et al, 2021 ) and breast cancer ( Hu et al, 2021 ). SUMOylation is also important for endocrinal thyroid hormone production ( Ke et al, 2021 ), has a cardiac protective role in heart failure and diabetic cardiomyopathy ( Liu et al, 2021 ; Wang et al, 2021b ) and plays a role in immunological responses and viral therapy ( Imbert and Langford, 2021 ; Sajeev et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The Hydrogen-Coupled Oligopeptide Membrane Cotransporter Pept2 is SUMOylated in Kidney Distal Convoluted Tubule Cells

Aroankins

Murali

Fenton

et al. 2021

Front. Mol. Biosci.

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Protein post-translational modification by the Small Ubiquitin-like MOdifier (SUMO) on lysine residues is a reversible process highly important for transcription and protein stability. In the kidney, SUMOylation appears to be important for the cellular response to aldosterone. Therefore, in this study, we generated a SUMOylation profile of the aldosterone-sensitive kidney distal convoluted tubule (DCT) as a basis for understanding SUMOylation events in this cell type. Using mass spectrometry-based proteomics, 1037 SUMO1 and 552 SUMO2 sites, corresponding to 546 SUMO1 and 356 SUMO2 proteins, were identified from a modified mouse kidney DCT cell line (mpkDCT). SUMOylation of the renal hydrogen-coupled oligopeptide and drug co-transporter (Pept2) at one site (K139) was found to be highly regulated by aldosterone. Using immunolabelling of mouse kidney sections Pept2 was localized to DCT cells in vivo. Aldosterone stimulation of mpkDCT cell lines expressing wild-type Pept2 or mutant K139R-Pept2, post-transcriptionally increased Pept2 expression up to four-fold. Aldosterone decreased wild-type Pept2 abundance in the apical membrane domain of mpkDCT cells, but this response was absent in K139R-Pept2 expressing cells. In summary, we have generated a SUMOylation landscape of the mouse DCT and determined that SUMOylation plays an important role in the physiological regulation of Pept2 trafficking by aldosterone.

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Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review)

Cited by 7 publications

References 205 publications

Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival

Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and Promotes Leishmania donovani Survival

Oxygen‐regulated post‐translation modifications as master signalling pathway in cells

The Hydrogen-Coupled Oligopeptide Membrane Cotransporter Pept2 is SUMOylated in Kidney Distal Convoluted Tubule Cells

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