Browsing by Subject "Site directed mutagenesis"

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Open Access
Electronic excited states of the CP29 antenna complex of green plants: a model based on exciton calculations
(Springer / Kluwer Academic Publishers, 2000) İşerı, E. İ.; Albayrak, D.; Gülen, D.
We have suggested a model for the electronic excited states of the minor plant antenna, CP29, by incorporating a considerable part of the current information offered by structure determination, site-directed mutagenesis, and spectroscopy in the modeling. We have assumed that the electronic excited states of the complex have been decided by the chlorophyll-chlorophyll (Chl) and Chl-protein interactions and have modeled the Coulombic interaction between a pair of Chls in the point-dipole approximation and the Chl-protein interactions are treated as empirical fit parameters. We have suggested the Qy dipole moment orientations and the site energies for all the chlorophylls in the complex through a simultaneous simulation of the absorption and linear dichroism spectra. The assignments proposed have been discussed to yield a satisfactory reproduction of all prominent features of the absorption, linear and circular dichroism spectra as well as the key spectral and temporal characteristics of the energy transfer processes among the chlorophylls. The orientations and the spectral assignments obtained by relatively simple exciton calculations have been necessary to provide a good point of departure for more detailed treatments of structure-function relationship in CP29. Moreover, it has been discussed that the CP29 model suggested can guide the studies for a better understanding of the structure-function relationship in the major plant antenna, LHCII.
Open Access
The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelialmesenchymal transition in breast cancer
(Impact Journals LLC, 2016) Raza, U.; Saatci, O.; Uhlmann, S.; Ansari, S. A.; Eyüpoglu, E.; Yurdusev, E.; Mutlu, M.; Ersan, P. G.; Altundağ, M. K.; Zhang, J. D.; Dogan, H. T.; Güler, G.; Şahin, Ö.
Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPRCas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a 'molecular switch' between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53- mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis.