Posttranslational regulation of neurofibromin content in melanocytes of neurofibromatosis type 1 patients.
Neurofibromatosis type 1 (NF1) is a common autosomal dominantly inherited disorder characterized by neurofibromas and café-au-lait macules. Most of the NF1 gene germline mutations result in a reduction in the level of neurofibromin. As shown recently, the neurofibromin level can be regulated posttranslationally through alteration of the protein half-life. This raises the question as to whether this type of regulation is also operating in cultured melanocytes of NF1 patients especially in melanocytes derived from café-au-lait macules. In melanocytes cultured without phorbol 12-myristate 13-acetate (PMA) the neurofibromin half-lives were 24 h (healthy controls, MC), 26 h (apparently healthy skin of NF1 patients, MNFS) and 25 h (café-au-lait macules of NF1 patients, MNFC). In PMA-stimulated cells the neurofibromin half-lives were 68 h (MC) and 73 h (MNFS) whereas it was 45 h in melanocytes derived from NF1 café-au-lait macules. The amount of NF1 mRNA was not altered under these culture conditions as shown by competitive RT-PCR. We speculate that this regulation is involved in the formation of some NF1 symptoms, for instance in the formation of café-au-lait macules.
Kaufmann
D
D
Abteilung Humangenetik, Universität Ulm, Germany. dieter.kaufmann@medizin.uni-ulm.de
Bartelt
B
B
Hoffmeyer
S
S
Müller
R
R
D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D006207:Half-Life; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025542:Neurofibromin 1; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D025542:Neurofibromin 1; D011506:Proteins; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate