Disease relevance of Gnl3

• The profiles of adenylate cyclase activity responsiveness of certain variants to guanosine-5'-(beta, gamma-imido) triphosphate and to forskolin resembled those of UNC and cyc phenotypes of S49 lymphoma cells, which are functionally deficient in the GTP-sensitive coupling protein, Ns [1].
• The amount of the stimulatory regulatory component, Ns, in fat cell membranes is not altered by hypothyroidism (Malbon, C. C., Graziano, M. P., and Johnson, G. L. (1984) J. Biol. Chem. 259, 3254-3260) [2].
• RCAP may facilitate coupling between Ns and the catalytic unit of adenylate cyclase by a pertussis toxin-like effect to inactivate Ni [3].
• In fact, two guanine nucleotide regulatory proteins, Ns and Ni, coexisted in the soluble complex as established by identifying the 42-kDa subunit of Ns and the 40-kDa subunit of Ni, after ADP-ribosylation by cholera toxin and Bordetella pertussis toxin, respectively [4].
• Exotoxins of Vibrio cholerae and Bordetella pertussis were used to determine respectively the involvement of the stimulatory and inhibitory guanine nucleotide-binding regulatory components (Ns and Ni) in NaCl inhibition [5].

High impact information on Gnl3

• Depletion or overexpression of nucleostemin reduces cell proliferation in CNS stem cells and transformed cells [6].
• When stem cells differentiate, nucleostemin expression decreases rapidly prior to cell-cycle exit both in vitro and in vivo [6].
• The data indicate that lesion-induced dopaminergic sprouting in the olfactory tubercle is temporally coordinated with the increased formation of dopamine receptors, both D1 and D2, the stimulatory guanine nucleotide regulatory protein (Ns) and the catalytic subunit (C) of adenylate cyclase in the postsynaptic membrane [7].
• Furthermore, nucleostemin was excluded from the nucleolar domains in which ribosomes are born--the fibrillar centers and dense fibrillar component [8].
• We found the dynamic properties of nucleostemin differed strikingly from fibrillarin (a protein directly involved in rRNA processing) both in response to rRNA transcription inhibition and in the schedule of reentry into daughter nuclei and the nucleolus during late telophase/early G1 [8].

Chemical compound and disease context of Gnl3

• Finally, the capacity of Ns solubilized from treated membranes to stimulate adenylate cyclase activity when reconstituted into cyc- S49 lymphoma cell membranes was enhanced by approximately 50% compared to control [9].

Biological context of Gnl3

• Nucleostemin, a novel p53 binding protein localized in the nucleoli of ESCs, is not expressed in the differentiated cells of adult tissue, suggesting a role in maintaining stem cell self-renewal [10].
• Furthermore, TRH regulation of polyphosphoinositide hydrolysis is modulated by guanine nucleotides; however, nucleotide regulation appears to involve a GTP-binding factor (Np) other than Ns or Ni [11].
• These results indicate that isoproterenol caused homologous desensitization consisting of only a "down regulation" of the beta-adrenergic receptor, whereas glucagon caused heterologous desensitization, mainly by alteration of the Ns component, as well as "down regulation" of glucagon receptor [12].
• The dual effects of RCAP upon ADP-ribosylation of Ni and Ns alpha subunits suggest that a binding site for RCAP may exist at a site of homology between Ns alpha and Ni alpha [3].
• These findings showed that there is an abnormal signal transduction in this system in SHR due to a reduction in the functional activity of alpha-subunits of Ns [13].

Anatomical context of Gnl3

• Nucleostemin, a coordinator of self-renewal, is expressed in rat marrow stromal cells and turns off after induction of neural differentiation [10].
• Concurrently, the quantity of label incorporated by cholera toxin into the alpha subunit of the stimulatory guanine nucleotide regulatory protein (Ns) was increased by 44 +/- 14% in treated membranes [9].
• Heterologous desensitization of the inhibitory A1 adenosine receptor-adenylate cyclase system in rat adipocytes. Regulation of both Ns and Ni [9].
• Furthermore, the potentiating action of phenylephrine was observed following 90 min but not 20 min of cholera toxin pretreatment. these results suggest that the regulation of cyclic GMP levels in the pineal gland involves an Ns-like GTP-binding regulatory protein [14].
• Similar to its effects in rat reticulocytes, RCAP inhibited ADP-ribosylation of Ns and enhanced ADP-ribosylation of Ni [3].

Associations of Gnl3 with chemical compounds

• Many lines of evidence indicate that the light component (Mr = 52,000) is the VIP-receptor complex while the heavy component (Mr = 150,000) is a ternary complex consisting of VIP, the receptor, and a guanine nucleotide regulatory protein, probably Ns [15].
• Thus, the direct inhibition of the catalyst by beta gamma or GTP gamma S-bound alpha 41 is a likely mechanism involved in receptor-mediated inhibition of adenylate cyclase, in addition to the previously proposed indirect inhibition due to the reduction of the concentration of the active alpha-subunit of Ns by reassociation with beta gamma [16].
• The apparent reduction in cardiac beta-adrenergic receptor number by NEM (in the absence of beta-receptor agonist) is compatible with a model in which part of the receptor population is able to undergo spontaneous coupling to Ns [17].
• Sucrose gradient centrifugation totally resolved the catalytic subunit from both functional Ni and stimulatory GTP regulatory component (Ns) activities [18].
• It thus seems that, besides its effect on the Ns system, ethanol may also impair Ni-mediated adenylate cyclase responses in rat cerebral cortex [19].

Other interactions of Gnl3

• In conclusion, our results suggest that nucleostemin, but not Oct-4 or Nanog, is expressed in BMSCs and it possibly regulates self-renewal proliferation in BMSCs [10].
• Expression of Neuro D and Cyclin D1 also diminish as differentiation proceeds but at much slower rates as compared to nucleostemin [10].

Analytical, diagnostic and therapeutic context of Gnl3

• In the present study, we have evaluated the expression profile of nucleostemin in rat BMSCs before and after the induction of neural differentiation by RT-PCR and immunocytochemistry [10].

References