TY  - JOUR
A1  - Schlag, Peter M.
A1  - Osterziel, Karl Joseph
A1  - Özcelik, Cemil
A1  - Scherneck, Siegfried
A1  - Wenzel, Katrin
A1  - Daskalow, Katjana
A1  - Herse, Florian
A1  - Seitz, Susanne
A1  - Zacharias, Ute
A1  - Schenk, Jörg A.
A1  - Schulz, Herbert
A1  - Hübner, Norbert
A1  - Micheel, Burkhard
T1  - The protein phosphatase 1 inhibitor KEPI is down regulated in breast cancer cell lines and tissues and involved in the regulation of the tumour suppressor EGR1 via the MEK-ERK pathway
N2  - KEPI is a protein kinase C-potentiated inhibitory protein for type 1 Ser/Thr protein phosphatases. We found no or reduced expression of KEPI in breast cancer cell lines, breast tumors and metastases in comparison to normal breast cell lines and tissues, respectively. KEPI protein expression and ubiquitous localization was detected with a newly generated antibody. Ectopic KEPI expression in MCF7 breast cancer cells induced differential expression of 95 genes, including the up-regulation of the tumor suppressors EGR1 (early growth response 1) and PTEN (phosphatase and tensin homolog), which is regulated by EGR1. We further show that the up-regulation of EGR1 in MCF7/KEPI cells is mediated by MEK-ERK signaling. The inhibition of this pathway by the MEK inhibitor UO126 led to a strong decrease in EGR1 expression in MCF7/KEPI cells. These results reveal a novel role for KEPI in the regulation of the tumor suppressor gene EGR1 via activation of the MEK-ERK MAPK pathway.
Y1  - 2008
UR  - http://www.atypon-link.com/doi/abs/10.1515/BC.2007.062
ER  - 
TY  - JOUR
A1  - Gehmlich, Katja
A1  - Geier, C.
A1  - Osterziel, Karl Joseph
A1  - Fürst, Dieter Oswald
T1  - Mutant muscle LIM protein is associated with hypertrophic cardiomyopathy and exhibits altered binding properties in the system MLP - N-RAP - alpha-actinin
Y1  - 2004
SN  - 0171-9335
ER  - 
TY  - JOUR
A1  - Gehmlich, Katja
A1  - Geier, C.
A1  - Osterziel, Karl Joseph
A1  - VanderVen, Peter F. M.
A1  - Fürst, Dieter Oswald
T1  - Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy
N2  - Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy. We show that MLP can form a ternary complex with two of its previously documented myofibrillar ligand proteins, N-RAP and alpha-actinin, which indicates the presence of distinct, non-overlapping binding sites. Our data also show that, in comparison to wild-type MLP, the capacity of the mutated MLP protein to bind both N-RAP and alpha-actinin is significantly decreased. In addition, this single point mutation prevents zinc coordination and proper folding of the second zinc-finger in the first LIM domain, which consequently renders the protein less stable and more susceptible to proteolysis. The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin. This assumption is supported by the previous observation that in the pathological situation accompanied by MLP down regulation, cardiomyocytes try to compensate for the decreased stability of MLP protein by increasing the expression of its ligand N-RAP, which might finally result in the development of myocyte disarray that is characteristic of this disease
Y1  - 2004
SN  - 0302-766X
ER  -