Disease relevance of POMC

• The system involved infection of cells with a recombinant vaccinia virus carrying the T7 RNA polymerase gene and transfection with a plasmid containing the mouse POMC sequence flanked by the T7 RNA polymerase promoter at its 5'-end and the T7 RNA polymerase terminator at its 3'-end [1].
• The recombinant prohormones proenkephalin, proneuropeptide Y (pro-NPY), and proopiomelanocortin (POMC) were expressed in Escherichia coli using the T7 expression system and purified for in vitro processing studies [2].
• 1-28-POMC stimulated cell proliferation in human NCI-h295 and mouse Y-1 adrenal cancer cell lines and also in primary cultures of bovine adrenocortical cells in a concentration-dependent manner [3].
• This probe hybridizes specifically to a species of poly(A)-RNA from adrenal medulla and human pheochromocytoma, (1400--1450 bases), and also to [Met]enkephalin-containing pro-opiomelanocortin mRNAs from bovine pituitary (1200 bases) and from mouse pituitary tumor cell (1100 bases) [4].
• Pro-opiomelanocortin gene expression and peptide secretion in human small-cell lung cancer cell lines [5].

High impact information on POMC

• These and other observations have suggested that POMC peptides are synthesized locally in the medial basal hypothalamus and reach other regions of the CNS by axonal transport [6].
• A major question concerning brain POMC is whether it is synthesized within the central nervous system (CNS) itself or whether it is taken up from plasma flowing in a retrograde fashion from the pituitary [6].
• Ardrenocorticotropic hormone (ACTH), beta-endorphin and the melanotropins (MSHs) are all derived from a single large precursor molecule, proopiomelanocortin (POMC) by individual processing through a series of co- and post-translational modifications [6].
• POMC peptides have been detected immunohistochemically and biochemically in the medial basal hypothalamus, the amygdala and throughout the brain stem [6].
• This sequence confirmed the known structure of the carboxyl half of POMC and revealed the presence of a new MSH-like moiety, gamma-MSH, within the 16,000-MW amino half of the precursor (16K fragment) [7].

Chemical compound and disease context of POMC

• ACTH1-24 (5 ng/min per kg, i.v.) increased the output of cortisol from the adrenal by about 500 ng/min per kg body weight and this effect was rapidly reduced by simultaneous infusion of ovine proopiomelanocortin at 5 ng/min per kg [8].

Biological context of POMC

• The POMC gene is expressed in the hypothalamus of postpartum anestrus cows with POMC mRNA levels higher (P<0.05) in the hypothalamus than in the preoptic region [9].
• Post-translational modification of bovine pro-opiomelanocortin. Tyrosine sulfation and pyroglutamate formation, a mass spectrometric study [10].
• POMC mRNA was amplified by reverse transcriptase-polymerase chain reaction using anti-sense and sense primers designed from Exons 2 and 3 of POMC gene [11].
• The results of segregation analysis of mink POMC sequences and mink chromosomes in the mink-Chinese hamster panel allowed us to assign the POMC gene to mink chromosome 11 [12].
• These data provide the first functional evidence to support a role for differential O-linked glycosylation in the regulation of the processing of the N-terminus of bovine POMC [13].

Anatomical context of POMC

• Disruption of both disulfide bridges or the second disulfide bridge or removal of the amphipathic hairpin loop resulted in constitutive secretion of the mutant POMC from the cells and a lack of punctate secretory granule immunostaining within the cells [14].
• We have previously demonstrated the presence of unique oligosaccharides terminating with GalNAc-4-SO4 on the pituitary glycoproteins lutropin (LH), thyroid stimulating hormone (TSH), and pro-opiomelanocortin (POMC) [15].
• The data also indicate the existence of subsets of POMC neurons within the arcuate nucleus [16].
• In this study, in situ hybridization with anti-sense cRNA riboprobe was used to show expression of POMC mRNA in human epidermis and cultured human epidermal cells (melanocytes and keratinocytes) [11].
• Extensive intermingling of LHRH and POMC fibers occurred within zona externa of the median eminence [17].

Associations of POMC with chemical compounds

• Covariate analysis indicated (P = 0.10) that as mean serum LH concentrations increased, hypothalamic POMC mRNA levels decreased [9].
• The cDNA sequence for bovine pro-opiomelanocortin predicts the presence of glutamic acid at position 1 of both peptides [10].
• We have modeled the NH2-terminal POMC Cys8 to Cys20 domain and have identified it as an amphipathic loop containing four highly conserved hydrophobic and acidic amino acid residues (Asp10-Leu11-Glu14-Leu1) [14].
• The NH2-terminal region of pro-opiomelanocortin (POMC) is highly conserved across species, having two disulfide bridges that cause the formation of an amphipathic hairpin loop structure between the 2nd and 3rd cysteine residues (Cys8 to Cys20) [14].
• To determine whether the inhibitory effect of GABA could be accounted for by a direct action on POMC neurons, we investigated the localization of the beta 1-subunit of the GABAA-benzodiazepine-receptor complex in the arcuate nucleus [16].

Physical interactions of POMC

• CPE has been shown to bind to an amino-terminal peptide of pro-opiomelanocortin (N-POMC) at pH 5.5 and hypothesized to be critically involved in the targeting of hormones such as POMC to the regulated secretory pathway [Cool, D. R., Normant, E., Shen, F., Chen, H. C., Pannell, L., Zhang, Y., and Loh, Y. P. (1997) Cell 88, 73-83] [18].

Regulatory relationships of POMC

• Production of pro-opiomelanocortin (POMC) by a vaccinia virus transient expression system and in vitro processing of the expressed prohormone by POMC-converting enzyme [1].

Other interactions of POMC

• Because both CRH and POMC regulate appetite, potential interaction effects between these two genes were assessed [19].
• In contrast, the 70-kDa aspartic proteinase cleaved POMC most readily, with cleavage of proenkephalin and some processing of pro-NPY [2].
• N-POMC1-26, which contains the POMC sorting signal, bound to CPE in the SG membranes with low affinity and the binding was ion independent [20].
• In cryosections of embryonic chicken adenohypophyses, from day 10, distinct cell populations gradually become immunoreactive to chicken-specific monoclonal antibodies against proopiomelanocortin, the beta-subunit of luteinizing hormone, growth hormone, and prolactin [21].

Analytical, diagnostic and therapeutic context of POMC

• The chicken POMC coding region appears to consist of 678 base pairs in the pituitary and also in the hypothalamus, as assessed by reverse transcriptase PCR [22].
• As assessed by Northern blot analysis, the length of the POMC mRNA in both the pituitary and the hypothalamus was approximately 1,200 nucleotides [22].
• Labeling the transfected cells with [3H]Arg, followed by immunoprecipitation and SDS-PAGE showed the synthesis of a major peak of POMC, 33 kDa [1].
• The immunoassay developed should be valuable in understanding the disposition and processing in this specific region of POMC [23].
• Peptide mapping and amino acid analysis indicated that the primary sequence corresponds exactly to that predicted by cDNA techniques for the first 49 residues of POMC including the presence of four cysteine residues [24].

References