Disease relevance of SCG2

• Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors [1].
• After treatment with phorbol 12-myristate 13-acetate (10(-7) M) for 7 days, there was an increase in the mRNA for CgB and SgII mRNAs in GH and null cell tumors, while dexamethasone treatment for 7 days increased CgA mRNA in GH and null cell adenomas [2].
• Interestingly, cAMP had no effect upon secretogranin II gene transcription in PC12 and neuroblastoma cells [3].
• Our results indicate that SgII may represent not only a valuable histological marker for non-functioning pituitary adenomas, but also a pertinent tool to study the proteolytic processing mechanisms in various neuroendocrine tumors [4].
• Basal as well as cAMP-stimulated transcription, directed from the secretogranin II promoter was, however, impaired in insulinoma cells by overexpression of CREB-2, a negative-acting CRE-binding protein [3].
• SgII represents a key AP-1-regulated protein that counteracts NO toxicity and mediates neuronal differentiation of neuroblastoma cells [5].

Psychiatry related information on SCG2

• Biochemical characterisation and immunohistochemical localisation of the secretogranin II-derived peptide EM66 in the hypothalamus of the jerboa (Jaculus orientalis): modulation by food deprivation [6].

High impact information on SCG2

• Two distinct populations of vesicles were formed: immature secretory granules containing secretogranin II and constitutive secretory vesicles containing the heparan sulfate proteoglycan [7].
• Identification of gastroenteropancreatic neuroendocrine cells in normal and neoplastic human tissue with antibodies against synaptophysin, chromogranin A, secretogranin I (chromogranin B), and secretogranin II [8].
• Granule formation, and the sorting of SgII and PC2 from the trans-Golgi network into ISGs and MSGs, however, is not affected [9].
• Analysis of the various secretory vesicles derived from the trans-Golgi network (TGN) indicated that DTT treatment diverted newly synthesized chromogranin B to constitutive secretory vesicles, whereas the packaging of secretogranin II into immature secretory granules was unaffected by the reducing agent [10].
• The kinetics of secretion of secretogranin II, as well as those of a constitutively secreted heparan sulfate proteoglycan, were reduced by treatment of PC12 cells with nocodazole, suggesting that both secretory granules and constitutive secretory vesicles are transported to the plasma membrane along microtubules [11].

Chemical compound and disease context of SCG2

• The finding of strongly reduced mRNA levels in upd(15)mat cells of the gene encoding secretogranin II (SCG2), which is a precursor of the dopamine releasing factor secretoneurin, raises the question whether hyperphagia in patients with PWS might be due to a defect in dopamine-modulated food reward circuits [12].
• Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: neuroendocrine expression in patients untreated and treated with androgen deprivation therapy [13].

Biological context of SCG2

• One of the novel genes that we identified, SCG2, proved to be identical to the recently published MEN1 gene, which is likely to be a tumour suppressor gene [14].
• In addition, a constitutively active mutant of ATF2 specifically transactivated a secretogranin II promoter/luciferase reporter gene, but had no effect on the tyrosine hydroxylase promoter [15].
• Using recombinant proteins we show that CREB2 binds in vitro to the palindromic cAMP response element derived from the secretogranin II gene [16].
• Synergistic action of upstream elements and a promoter-proximal CRE is required for neuroendocrine cell-specific expression and second-messenger regulation of the gene encoding the human secretory protein secretogranin II [17].
• Transfection analysis revealed that cAMP-induced transcription of the secretogranin II promoter/beta-globin gene in septal and insulinoma cells [3].

Anatomical context of SCG2

• The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also being present in the pancreas and thymus [14].
• The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH- and calcium-induced aggregation [18].
• Taken together, these data demonstrate that posttranslational processing of SgII actually generates EM66 in the adrenal gland [19].
• To investigate the functional significance of this motif, intracellular cAMP levels were increased in a neuronal cell line derived from the septal region of the brain and the level of secretogranin II gene expression was analysed [3].
• In the majority of differentiated cells, a clearly punctate SgII immunolabeling indicative of the presence of secretory organelles was present in the Golgi region, at the cell periphery, along the neurites and in growth cones [20].

Associations of SCG2 with chemical compounds

• In vivo, ammonium chloride, which is known to neutralize the pH of acidic intracellular compartments, inhibited the packaging of newly synthesized secretogranin II into secretory granules [18].
• Analysis of a 2.35-kilobase cDNA clone isolated from a human pituitary library and identified as secretogranin II by various criteria showed that human presecretogranin II is a 617-residue polypeptide containing an NH2-terminal located signal peptide [18].
• Secretoneurin (SN), a 33-amino acid neuropeptide, is derived from secretogranin II that is released from sensory afferent C-fibers by capsaicin [21].
• The transfer of SgII from the sulfation site to this distal compartment of the TGN involves BFA-sensitive membrane dynamics [22].
• In this study, we have investigated the subcellular compartment in which the cleavage of SgII is initiated by taking advantage of its tyrosine sulfation in the trans-Golgi network (TGN) [22].

Other interactions of SCG2

• Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II [23].
• Immunolocalization of secretogranin II, chromogranin A, and chromogranin B in differentiating human neuroblastoma cells [20].
• DNA-protein binding assays showed that recombinant CRE-binding protein (CREB), produced in bacteria or human cells, bound in a sequence-specific manner to the secretogranin II promoter CRE [3].
• In primary tumors, sst2 was positively related to the expression of the neuroendocrine marker secretogranin II (P < 0.05) and negatively related to N-myc amplification (a poor prognostic factor, P < 0.005) and metastatic dissemination (P < 0.05) [24].
• Immunocytochemical experiments show that not all of the vesicles that express synaptotagmin l contain secretogranin II [25].

Analytical, diagnostic and therapeutic context of SCG2

• Molecular cloning of secretogranin II (SgII) in phylogenetically distant species has recently revealed the existence of a highly conserved 66-amino acid peptide flanked by preserved pairs of basic residues [19].
• In the present report, a specific hSgII antiserum was used in immunohistochemistry experiments to determine the distribution of SgII in normal anterior pituitaries and pituitary adenomas (5 gonadotroph, 3 non-functioning and 5 mammotroph tumors) [4].
• Northern blot analyses demonstrated the same 2.5 kb SgII mRNA species in all types of tumors as in normal anterior pituitaries [4].
• Western blotting experiments revealed that both the 46 K and 31 K polypeptides arose from the second half (C-terminal) of the molecule, thus suggesting that SgII may be processed by cleavage of short N-terminal polypeptides not detected in our conditions [4].
• Sequence analysis revealed the existence of numerous putative cis-regulatory elements in the SgII gene promoter, including a consensus cyclic AMP-responsive element (CRE) [17].

References