The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21<sup>WAF1</sup>

Kim, KyeongJin; Choi, Yoon Ha; Kim, Hyeong Hoe; Cheong, JaeHun

doi:10.3858/emm.2009.41.6.048

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…Indeed, while SHP was firstly described as transcriptional co-activator of NF-κB in several cell types [21][22][23][24], data from others support an anti-inflammatory role for this nuclear receptor [18][19][20]. Specifically, the molecular mechanisms by which SHP drives its antiinflammatory effects involved dual regulatory functions in a canonical transcription factor NF-κB signalling pathway, acting as both a repressor of transactivation of the NF-κB subunit p65…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…In the heart, SHP expression blocks cardiac hypertrophy by interfering with GATA binding protein 6 (GATA6) signalling [17]. Concerning the role of SHP in the regulation of the inflammatory response, conflicting results have been reported in different contexts, i.e., SHP exerts anti-inflammatory effects [18][19][20], and SHP takes part in NF-κB activation [21][22][23][24]. In particular, the role of this nuclear receptor in cardiac glucose/lipid metabolism and inflammation is understudied.…”

Section: Introductionmentioning

confidence: 99%

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Small heterodimer partner (SHP) contributes to insulin resistance in cardiomyocytes

Rodríguez-Calvo

Chanda

Oligschlaeger

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM). In addition, SHP overexpression increased Socs3 mRNA and reduced IRS-1 protein levels. SHP overexpression also induced Cd36 expression (~6.2 fold; p<0.001) linking to the observed intramyocellular lipid accumulation. SHP overexpressing cells further showed altered expression of genes involved in lipid metabolism, i.e., Acaca, Acadvl or Ucp3, augmented NF-κB DNA-binding activity and induced transcripts of inflammatory genes, i.e., Il6 and Tnf mRNA (~4-fold induction, p<0.01). Alterations in metabolism and inflammation found in SHP overexpressing cells were associated with changes in the mRNA levels of Ppara (79% reduction, p<0.001) and Pparg (~58-fold induction, p<0.001). Finally, co-immunoprecipitation studies showed that SHP overexpression strongly reduced the physical interaction between PPARα and the p65 subunit of NF-κB, suggesting that dissociation of these two proteins is one of the mechanisms by which SHP initiates the inflammatory response in cardiac cells. Overall, our results suggest that SHP upregulation upon high-fat feeding leads to lipid accumulation, insulin resistance and inflammation in cardiomyocytes.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Small heterodimer partner (SHP) contributes to insulin resistance in cardiomyocytes

Rodríguez-Calvo

Chanda

Oligschlaeger

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Multiple studies revealed that when SHP specific ligands, 5-Cl-AHPN & 3-Cl-AHPC used alone or in combination, decreased cell proliferation and increased cell cycle arrest, and apoptosis in KG-1 AML cells [ 127 , 128 ]. Kim et al (2009) reported that treatment of leukemic (U937) cells with differentiation agents such as phorbol esters (PMA) have increased the levels of SHP, p21 WAF1 , and p65 of NF-κB subunits, suggesting how the expression of SHP increases the cellular survival of differentiating monocytes by transcriptional regulation of target genes of cell survival and differentiation [ 126 ]. In conclusion, SHPs play a vital role in tumorigenesis by modulating apoptosis, differentiation, and proliferation of tumor cells.…”

Section: Nrs In Hmmentioning

confidence: 99%

Exploring the nexus of nuclear receptors in hematological malignancies

Manickasamy,

Sajeev,

BharathwajChetty

et al. 2024

Cell. Mol. Life Sci.

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Hematological malignancies (HM) represent a subset of neoplasms affecting the blood, bone marrow, and lymphatic systems, categorized primarily into leukemia, lymphoma, and multiple myeloma. Their prognosis varies considerably, with a frequent risk of relapse despite ongoing treatments. While contemporary therapeutic strategies have extended overall patient survival, they do not offer cures for advanced stages and often lead to challenges such as acquisition of drug resistance, recurrence, and severe side effects. The need for innovative therapeutic targets is vital to elevate both survival rates and patients' quality of life. Recent research has pivoted towards nuclear receptors (NRs) due to their role in modulating tumor cell characteristics including uncontrolled proliferation, differentiation, apoptosis evasion, invasion and migration. Existing evidence emphasizes NRs' critical role in HM. The regulation of NR expression through agonists, antagonists, or selective modulators, contingent upon their levels, offers promising clinical implications in HM management. Moreover, several anticancer agents targeting NRs have been approved by the Food and Drug Administration (FDA). This review highlights the integral function of NRs in HM's pathophysiology and the potential benefits of therapeutically targeting these receptors, suggesting a prospective avenue for more efficient therapeutic interventions against HM. Graphical abstract

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“…Another recent study shows that SHP expression was increased during monocytic differentiaton through c-Jun and p65 mediated transcriptional activation of the SHP promoter [40]. Interestingly, SHP protected differentiated monocytic cells from etoposide-induced cellular apoptosis through the induction and cytoplasmic sequestration of p21WAF1.…”

Section: Shp and Apoptosismentioning

confidence: 99%

Nuclear Receptor Small Heterodimer Partner in Apoptosis Signaling and Liver Cancer

Zhang

Wang

2011

Cancers

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Small heterodimer partner (SHP, NR0B2) is a unique orphan nuclear receptor that contains the dimerization and a putative ligand-binding domain, but lacks the conserved DNA binding domain. SHP exerts its physiological function as an inhibitor of gene transcription through physical interaction with multiple nuclear receptors and transcriptional factors. SHP is a critical transcriptional regulator affecting diverse biological functions, including bile acid, cholesterol and lipid metabolism, glucose and energy homeostasis, and reproductive biology. Recently, we and others have demonstrated that SHP is an epigenetically regulated transcriptional repressor that suppresses the development of liver cancer. In this review, we summarize recent major findings regarding the role of SHP in cell proliferation, apoptosis, and DNA methylation, and discuss recent progress in understanding the function of SHP as a tumor suppressor in the development of liver cancer. Future study will be focused on identifying SHP associated novel prooncogenes and anti-oncogenes in liver cancer progression and applying the knowledge gained on SHP in liver cancer prevention, diagnosis and treatment.

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The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21^WAF1

Cited by 6 publications

References 43 publications

Small heterodimer partner (SHP) contributes to insulin resistance in cardiomyocytes

Small heterodimer partner (SHP) contributes to insulin resistance in cardiomyocytes

Exploring the nexus of nuclear receptors in hematological malignancies

Nuclear Receptor Small Heterodimer Partner in Apoptosis Signaling and Liver Cancer

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The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21WAF1

Cited by 6 publications

References 43 publications

Small heterodimer partner (SHP) contributes to insulin resistance in cardiomyocytes

Small heterodimer partner (SHP) contributes to insulin resistance in cardiomyocytes

Exploring the nexus of nuclear receptors in hematological malignancies

Nuclear Receptor Small Heterodimer Partner in Apoptosis Signaling and Liver Cancer

Contact Info

Product

Resources

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The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21^WAF1