Browsing by Author "Jabbar, Javaid"

Now showing 1 - 3 of 3

Open Access
Ankaferd Hemostat affects etoposide resistance of the malignant melanoma cells
(Akademi Doktorlar Yayınevi, 2020) Ghasemi, M.; Okay, M.; Malkan, Ü. Y.; Türk, S.; Jabbar, Javaid; Hocaoğlu, H.; Haznedaroğlu, İ. C.
The development of resistance towards chemotherapeutic drugs has become an obstacle in treatment of cancer. Ankaferd Hemostat [ABS] has shown to suppress the proliferation of melanoma cells, but little is known about its’ mechanism. In this study, we demon¬strate that ABS can make some melanoma cell lines such as A2058 more sensitive towards etoposide by altering the genes involved in oxidative phosphorylation [OXPHOS] pathway. ABS treatment has shown to increase the sensitivity of A2058 towards etoposide and showed no effect for SK-MEL-5. Previously known to be more resistant to etoposide, SK-MEL-30 showed least amount of sen¬sitivity to ABS. We found mitochondrion cluster to be the most relevant to genes altered by ABS. To validate our claim, we compared two sets of melanoma cell lines; A375 with A2058 and A375 with SK-MEL-2. The clusters that we obtained from A375 and A2058 comparison did contain mitochondrial related clusters, their corresponding p value was not significant. Whereas, the clusters from A375 and SK-MEL-2 comparison contain 72 genes in ‘oxidoreductase’ cluster with enrichment score of 2.52. To get insight of the oxidoreductase cluster, we put the genes in that cluster to Enrichr. We found that majority of the genes among oxidoreductase cluster participate in oxidative phosphorylation and electron transport chain. Our study suggests that the use of ABS prior to etoposide treat¬ment can increase the response of melanoma cell lines because of the alteration of OXPHOS genes.
Restricted
The Founding of aiesec in Ankara, its history, and its role in students’ life
(Bilkent University, 2016) Jabbar, Javaid; Dimo, Zoela; Tekriti, Youssef; Danilyuk, Tamara; Bayramov, Kamran
Open Access
POLR2A/RPB1 subunit of RNA polymerase II interacts with NTDMED14 containing core mediator complex to facilitate basal and activator driven transcription
(2020-06) Jabbar, Javaid
The Metazoan Mediator is a 2-MDa protein complex that consist of 30 subunits, most of which are evolutionarily conserved from yeast to humans8. The maintenance and regulation of the cell is dependent on spatiotemporal control of RNA polymerase II (Pol II) mediated transcription as a result of intrinsic and extrinsic signals. Perturbations caused by the environment and genetics can alter the fate of the cells and can lead to many diseases such as cancer. The role of Mediator is critical in maintaining the cellular environment as it relays signal to RNA polymerase II to regulate homeostasis, cell growth, cell differentiation and development. Thus, it is essential to understand the mechanism by which Mediator regulates the expression of Pol II genes. We have utilized Multibac expression system to synthesize recombinant protein subcomplexes of Mediator and Pol II subunits to elucidate the interaction surface between core Mediator complex and RNA Polymerase II. Our data indicates that POLR2A (RPB1) subunit of Pol II interacts with ~84 kDa N terminal region of Med14 (NTD-Med14) containing core Mediator complex. Furthermore, we also show that other subunits of Pol II including POLR2C (RPB3), POLR2D (RPB4), POLR2E (RPB5), POLR2F (RPB6), POLR2G (RPB7), POLR2H (RPB8), POLR2I (RPB9) POLR2L (RPB10), POLR2J (RPB11) and POLR2K (RPB12) does not interact with core Mediator complex. The binding assay also demonstrates that the recombinant RPB1 subunit competes with endogenous Pol II for the interaction with core Mediator, forming a stable RPB1-core Mediator protein complex. The interaction between RPB1 subunit and NTD-Med14 containing core Mediator complex is independent of Med26. We propose a model for Pol II recruitment to the promoter by core Mediator complex which demonstrates that NTD-Med14 of Core Mediator complex interacts with RPB1 subunit of RNA polymerase II and recruits it to the promoter to facilitate basal and activated transcription.