Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

mRNA that encodes the common peptide precursor for the hormones corticotropin and beta-lipotropin was purified from the neurointermediate lobe of bovine pituitaries, and double-stranded cDNA species synthesized from this template were cloned in Escherichia coli X1776 by inserting them into the Pst I endonuclease cleavage site of the pBR322 plasmid using poly(dG)poly(dC) homopolymeric extensions. Certain of the cloned cDNA inserts contain nucleotides corresponding to the complete amino acid sequence of bovine corticotropin and a coding sequence that corresponds to at least the first portion of bovine beta-lipotropin. The nucleotide sequences coding for corticotropin and beta-lipotropin are separated on the cDNA by a 6-base-pair sequence encoding lysine and arginine, indicating that the carboxyl terminus of corticotropin is connected on the precursor peptide with the amino terminus of beta-lipotropin by these two amino acids. In addition, the cloned cDNA insert is characterized by an unusually high C+G nucleotide base content as well as by a number of DNA sequence duplications.
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PMID:Construction of bacterial plasmids that contain the nucleotide sequence for bovine corticotropin-beta-lipotropin precursor. 21 7

To determine the degree of similarity between pituitary and lymphocyte proopiomelanocortin, the lymphocyte mRNA was reverse transcribed, cloned, and sequenced. Murine lymphocyte mRNA was first purified by oligo(dT)-cellulose affinity chromatography and was reverse transcribed by using a selective 3' antisense oligonucleotide primer directed at the boundary between the translated/nontranslated region on the 3' end of exon 3. This cDNA was then amplified in a polymerase chain reaction with selective primers containing Sal I and Kpn I restriction endonuclease sites. Amplified cDNA was then directionally ligated into M13mp18 and M13mp19 bacteriophage and was sequenced. The nucleotide sequence encoding this peptide was identical to that of mouse pituitary corticotropin (ACTH). Elevated levels of lymphocyte immunoreactive ACTH were then induced with bacterial lipopolysaccharide and the peptide(s) was purified by antibody affinity chromatography and reverse-phase high-performance liquid chromatography. The predominant immunoreactive ACTH species was approximately 3 kDa and its sequence was identical to pituitary ACTH(1-25). These results conclusively demonstrate that lymphocytes produce authentic ACTH and harbor its mRNA.
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PMID:Nucleotide and amino acid sequence of lymphocyte-derived corticotropin: endotoxin induction of a truncated peptide. 168 57

We describe the characteristics of pro-opiomelanocortin (POMC) mRNA synthesized by a human small cell lung cancer (SCLC) cell line that secretes a peptide immunoreactive with antibodies to the POMC-derived component, adrenocorticotropin. While no alteration in restriction endonuclease pattern or structure was found for the SCLC-derived pomc gene vs. the previously described human pomc gene cloned from a fetal liver library, Northern-blot analysis of SCLC RNA using pomc-derived probes showed a hybridizing transcript more than 300 nucleotides longer than POMC mRNA isolated from human pituitaries, as well as a pomc-gene-hybridizing mRNA the same length as pituitary-derived transcripts. 5' end mapping and primer extension analyses showed that the novel mRNA species is initiated at a site 371 bp upstream from the 5' end identified for pituitary-derived POMC mRNA. We conclude that synthesis of POMC transcripts occurs from an ordinarily quiescent promoter in the SCLC cell line we have studied, as well as from the pomc promoter normally used in pituitary cells.
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PMID:Initiation of pro-opiomelanocortin mRNA from a normally quiescent promoter in a human small cell lung cancer cell line. 255 57

The structural gene for diphtheria toxin, tox, has been modified at its Sph I site by the introduction of an oligonucleotide linker encoding a unique Pst I restriction endonuclease site and a synthetic oligonucleotide encoding alpha-melanocyte-stimulating hormone (alpha-MSH). The resulting fusion gene directs the expression of a diphtheria toxin-related alpha-MSH hybrid protein in which the diphtheria toxin receptor-binding domain has been replaced with alpha-MSH sequences. The chimeric toxin has been partially purified from periplasmic extracts of recombinant Escherichia coli K-12 and has been found to be selectively toxic for alpha-MSH receptor-positive human malignant melanoma NEL-M1 cells in vitro.
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PMID:Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein. 309 31

The introduction of small mutations instead of null alleles into the mouse genome has broad applications to the study of protein structure-function relationships and the creation of animal models of human genetic diseases. To test a simple mutational strategy we designed a targeting vector for the mouse proopiomelanocortin (POMC) gene containing a single nucleotide insertion that converts the initial tyrosine codon of beta-endorphin 1-31 to a premature translational termination codon and introduces a unique Hpal endonuclease restriction site. The targeting vector also contains a neo cassette immediately 3' to the last POMC exon and a herpes simplex virus thymidine kinase cassette to allow positive and negative selection. Homologous recombination occurred at a frequency of 1/30 clones of electroporated embryonic stem cells selected in G418 and gancyclovir. 10/11 clones identified initially by a polymerase chain reaction (PCR) strategy had the predicted structure without evidence of concatemer formation by Southern blot analysis. We used a combination of Hpa I digestion of PCR amplified fragments and direct nucleotide sequencing to further confirm that the point mutation was retained in 9/10 clones. The POMC gene was transcriptionally silent in embryonic stem cells and the targeted allele was not activated by the downstream phosphoglycerate kinase-1 promoter that transcribed the neo gene. Under the electroporation conditions used, we have demonstrated that a point mutation can be introduced with high efficiency and precision into the POMC gene using a replacement type vector containing a retained selectable marker without affecting expression of the allele in the embryonic stem cells. A similar strategy may be useful for a wide range of genes.
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PMID:Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker. 839 2

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. It has recently been reported that mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH. We analyzed the nucleotide sequences of exon 7 of the StAR gene in a Japanese CLAH patient with a karyotype of 47,XYY, and her parents. The patient was homozygous for a nonsense mutation Q258X, which changed codon 258 (CAG) encoding Gln to the stop codon TAG, and the her parents were heterozygous for the Q258X mutation. Since the Q258X mutation destroys a MvaI site normally present in the StAR gene sequence, we confirmed the Q258X mutation by means of the restriction endonuclease MvaI digestion of the PCR products. Endocrinological examinations of the parents revealed normal responses of adrenal steroid hormones to exogenous adrenocorticotropin administration, confirming the failure to detect the heterozygous carriers of CLAH by hormonal evaluation.
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PMID:Homozygous Q258X mutation in the steroidogenic acute regulatory gene in a Japanese patient with congenital lipoid adrenal hyperplasia. 927 22

Basal cell carcinoma and squamous cell carcinoma are the most frequent types of cancer in the United States and represent 75 percent and 20 percent, respectively, of all nonmelanoma skin cancers. Since ultraviolet radiation is implicated in their development, photoprotection is fundamental in their prevention. Additional preventive measures include identifying high-risk individuals for early detection along with using agents, such as retinoids, that are effective in decreasing the risk of premalignant cells further developing into carcinomas. Newer agents achieving this goal include perillyl alcohol, T4 endonuclease 5, DL-alpha-tocopherol, and alpha-difluoromethylornithine. Procedural modalities are currently the standard of treatment, but recent evidence has consistently shown that newer (nonsurgical) therapies, such as interferon, imiquimod, retinoids, and 5-fluorouracil, can be used effectively either as monotherapies or as adjuvants to those surgical modalities for the treatment of superficial nonmelanoma skin cancers and premalignant lesions. These newer therapies have achieved significant reductions in morbidity and mortality. Procedural modalities that have been evolving into important tools for the treatment of actinic keratosis and nonmelanoma skin cancers include photodynamic therapy and lasers. Nonsurgical therapies currently proving to be effective in clinical trials include ingenol mebutate and cyclooxygenase-2 inhibitors. Agents that are showing promising results in early phases of clinical trials include betulinic acid; hedgehog signaling pathway inhibitors, such as cyclopamine and GDC-0449; alpha-melanocyte-stimulating hormone analogs, such as afamelanotide; epidermal growth factor receptor inhibitors, such as gefitinib and erlotinib; anti-epidermal growth factor receptor monoclonal antibodies, such as cetuximab and panitumumab; and the 5-fluorouracil prodrug capecitabine.
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PMID:Nonsurgical innovations in the treatment of nonmelanoma skin cancer. 2072 48