Uwe Lenk

Cowen Europe · Strategic Consulting

Proteins that fail to fold properly as well as constitutive or regulated short-lived proteins of the endoplasmatic reticulum (ER) are subjected to proteolysis by cytosolic 26 S proteasomes. This process, termed ER-associated protein degradation (ERAD), has also been implicated in the generation of some important human disorders, for example, cystic...

Our attempts to produce some mammalian membrane proteins of interest to us in E. coli failed miserably. Therefore, we tried to synthesize these proteins in the rapid translation system (RTS), an E.coli-based cell-free system. The proteins selected for this feasibility study represent four classes of membrane proteins that are found in organelles, i...

Integral membrane and secretory proteins which fail to fold productively are retained in the endoplasmic reticulum and targeted for degradation by cytoplasmic proteasomes. Genetic and biochemical analyses suggest that substrates of this pathway must be dislocated across the membrane of the endoplasmic reticulum (ER) by a process requiring a functio...

In this study we demonstrate that the Deg1 degradation signal of the transcriptional repressor Matα2 confers compartment-specific turnover to a reporter protein. Rapid degradation of a Deg1-containing fusion protein is observed only when the reporter is efficiently imported into the nucleus. In contrast, a reporter that is constantly exported from...

Duchenne muscular dystrophy and its allelic disorder Becker muscular dystrophy are among the most common hereditary human pathologies (1:3500). Two thirds of the genomic alterations responsible for these diseases involve gross gene rearrangements such as deletions, and less frequently duplications. The remaining one third includes point mutations s...

We report the first C-terminal missense mutation in a Duchenne muscular dystrophy patient. A G10227A transition of the dystrophin gene was found which resulted in the substitution of a highly conserved cysteine at position 3340 within the second half of the dystroglycan-binding domain. Residual amounts of 427 kDa dystrophin were detected in western...

Studies of the coding region of the neuronal glutamate transporter of 6 amyotrophic lateral sclerosis (ALS) patients and 10 controls show an identical pattern of four reported amino acid variations. No mutations and polymorphisms were detected in 5 sporadic ALS patients and a single patient with the familial form of the disease.

Approximately one-third of the mutations responsible for Duchenne muscular dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-termin...

Non-isotopic single-strand conformation polymorphism (SSCP) and direct sequencing was used for carrier diagnosis in four families of DMD/BMD patients with previously characterized point mutations, leading to the identification of eight carriers and four non-carriers. When the mutation caused a distinctly altered migration pattern of the single stra...

More than 30% of Duchenne and Becker muscular dystrophy (DMD/BMD) patients have no gross DNA rearrangements like deletions or duplications. The large size of the coding sequence of the dystrophin gene (11 kilobases) complicates systematic identification of point mutations. Recently reported approaches based on genomic DNA or mRNA show that chemical...

Duchenne and Becker muscular dystrophies (DMD/BMD) are caused by mutations in the human dystrophin gene. About two-thirds of DMD/BMD patients exhibit gross rearrangements in the gene whereas the mutations in the remaining one third are thought to be point mutations or minor structural lesions. By means of various progressive PCR-based techniques hi...

Carrier determination is important for genetic counselling in DMD/BMD families. The detection of altered PCR amplified dystrophin mRNA fragments owing to deletions, insertions, or point mutations has increased the possibilities of carrier determination. However, problems may occur because of alternative splicing events. Here we present a family wit...

Berlin, Humboldt-Univ., Diss., 1994.