60 YEARS OF POMC: POMC: the consummate peptide hormone precursor

Clark, Adrian; Lowry, P. J.

doi:10.1530/jme-16-0016

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Proopiomelanocortin (POMC) is a precursor peptide that is encoded by the POMC gene on chromosome 2p23. The POMC gene consists of three exons containing scattered introns that is processed through tissue‐specific posttranslational processing by hormone proconverting enzymes to produce a variety of biologically active peptides, such as ACTH, prolipotropic hormone (β‐ and γ‐LPH), melanocyte‐stimulating hormone (α‐, β‐, and γ‐MSH), β‐endorphin, and methylthioenkephalin (Clark & Lowry, 2016). Genetic variation in the POMC gene may contribute to dysfunction of the HPA axis and ACTH in numerous psychiatric disorders (Boero et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

An analysis of POMC gene methylation and expression in patients with schizophrenia

Chen,

Qing,

Zou

et al. 2024

Intl J of Devlp Neuroscience

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Schizophrenia is a chronic mental disorder that affects millions of people and is believed to be caused by both environmental and genetic factors. Despite extensive research, the exact mechanisms underlying schizophrenia are still unclear. Studies have shown that numerous psychiatric disorders are associated with methylation of the POMC gene, which encodes adrenocorticotropic hormone, a critical player in the hypothalamic–pituitary–adrenal axis. However, the association between DNA methylation in POMC patients and schizophrenia remains unclear. In this study, we evaluated three fragments of the POMC promoter region, including 51 CpG sites, in the peripheral blood of schizophrenia patients and healthy controls. The POMC protein level was measured via enzyme‐linked immunosorbent assay (ELISA). The schizophrenia group exhibited significantly greater levels of methylation of the POMC gene than those in the control group. The methylation level of the POMC‐2 fragment was significantly greater in the patient group than in the control group. There were 17 significantly hypermethylated CpG sites in the patient group. After stratification by sex, POMC methylation levels were found to be significantly greater in male schizophrenia patients than in healthy controls; the methylation levels of POMC‐2 fragments were greater in the male patient group; nine CpG sites were significantly hypermethylated in the male patient group; and only one CpG site was significantly hypermethylated in the female patient group. The POMC protein level in patients was significantly lower than that in healthy controls. These findings demonstrate that the DNA methylation of POMC might be associated with the pathophysiology of schizophrenia. Overall, studying the correlation between POMC methylation and schizophrenia may contribute to the diagnosis and evaluation of neuropsychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

An analysis of POMC gene methylation and expression in patients with schizophrenia

Chen,

Qing,

Zou

et al. 2024

Intl J of Devlp Neuroscience

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“…Considerable knowledge has been amassed concerning the generation process and functions of bioactive peptides derived from POMC [1,4]. However, the biological activity of the joining peptide region (JP) remains unknown, despite extensive research on POMCderived hormones [1,5,6].…”

Section: Introductionmentioning

confidence: 99%

The Cell Adhesion Activity of the Joining Peptide of Proopiomelanocortin

Hiroshima,

Sakata,

Konogami

et al. 2023

Molecules

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Proopiomelanocortin (POMC) is a precursor protein of several peptide hormones, such as ACTH and β-endorphin. Almost all of the peptide hormones in POMC have been drastically investigated in terms of their biological activities. However, the biological activity of the joining peptide region (JP) in POMC is unknown. Therefore, to explore the biological activity of JP, sequence analyses of mammalian POMC were performed. We found an -Arg-Gly-Asp- (RGD) motif in several mammalian species, such as porcine, suggesting that JP has cell adhesion activity. To validate this hypothesis, the cell adhesion activities of the synthetic porcine JP peptides were examined using 293T cells. Cell adhesions were observed in a concentration-dependent manner of the JP peptides. In addition, the JP peptide competitively inhibited cell adhesion to the POMC-coated plates. Moreover, the cell adhesion activity of the joining peptide was inhibited by the addition of EDTA, indicating that the JP peptide mediates the cell adhesion activity via a receptor protein, integrin. Interestingly, a human JP peptide, which possesses an -Arg-Ser-Asp- (RSD) sequence in place of the RGD sequence, exhibited a higher ability in the cell adhesion activity than that of the porcine JP peptide, suggesting that the cell adhesion activity of the joining peptide is developed during the molecular evolution of POMC. In conclusion, our results reveal that the joining peptide in POMC plays an important role during cell adhesion and provide useful information related to signal transduction of nerve peptide hormones derived from POMC.

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“…Each of these peptides is synthesized from a newly synthesized precursor protein as it moves from its site of synthesis in the endoplasmic reticulum, through the secretory pathway lumen and into the secretory granules from which it is released in response to the appropriate combination of stimuli (Chrétien & Mbikay, 2016;Clark & Lowry, 2016;. A limited set of subtilisin-like endoproteases, carboxypeptidase B-like exoproteases and other post-translational processing enzymes convert these precursors, which are often inactive, into active products as they move through the secretory pathway (Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

“…Bioactive peptides play a key role in controlling many complex pathways, including blood glucose (insulin and glucagon, for example), salt and water balance (vasopressin, atrial natriuretic peptide), appetite (cholecystokinin, α‐melanocyte stimulating hormone, leptin), reproduction (gonadotropin hormone releasing hormone, follicle stimulating hormone) and gastrointestinal function (gastrin, motilin). Each of these peptides is synthesized from a newly synthesized precursor protein as it moves from its site of synthesis in the endoplasmic reticulum, through the secretory pathway lumen and into the secretory granules from which it is released in response to the appropriate combination of stimuli (Chrétien & Mbikay, 2016; Clark & Lowry, 2016; Kumar, Mains, & Eipper, 2016). A limited set of subtilisin‐like endoproteases, carboxypeptidase B‐like exoproteases and other post‐translational processing enzymes convert these precursors, which are often inactive, into active products as they move through the secretory pathway (Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

Peptidylglycine α‐amidating monooxygenase as a therapeutic target or biomarker for human diseases

Merkler

Hawley

Eipper

et al. 2022

British J Pharmacology

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Peptides play a key role in controlling many physiological and neurobiological pathways. Many bioactive peptides require a C‐terminal α‐amide for full activity. The bifunctional enzyme catalysing α‐amidation, peptidylglycine α‐amidating monooxygenase (PAM), is the sole enzyme responsible for amidated peptide biosynthesis, from Chlamydomonas reinhardtii to Homo sapiens. Many neuronal and endocrine functions are dependent upon amidated peptides; additional amidated peptides are growth promoters in tumours. The amidation reaction occurs in two steps, glycine α‐hydroxylation followed by dealkylation to generate the α‐amide product. Currently, most potentially useful inhibitors target the first reaction, which is rate‐limiting. PAM is a membrane‐bound enzyme that visits the cell surface during peptide secretion. PAM is then used again in the biosynthetic pathway, meaning that cell‐impermeable inhibitors or inactivators could have therapeutic value for the treatment of cancer or psychiatric abnormalities. To date, inhibitor design has not fully exploited the structures and mechanistic details of PAM.

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60 YEARS OF POMC: POMC: the consummate peptide hormone precursor

Cited by 8 publications

References 19 publications

An analysis of POMC gene methylation and expression in patients with schizophrenia

An analysis of POMC gene methylation and expression in patients with schizophrenia

The Cell Adhesion Activity of the Joining Peptide of Proopiomelanocortin

Peptidylglycine α‐amidating monooxygenase as a therapeutic target or biomarker for human diseases

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