scholarly journals Role of Cis Expression and Translational Coupling in the Assembly of a Functional Drug Pump

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Prajakta Pradhan ◽  
Parjit Kaur
2002 ◽  
Vol 184 (20) ◽  
pp. 5772-5780 ◽  
Author(s):  
J. Praszkier ◽  
A. J. Pittard

ABSTRACT Replication of the IncB miniplasmid pMU720 requires synthesis of the replication initiator protein, RepA, whose translation is coupled to that of a leader peptide, RepB. The unusual feature of this system is that translational coupling in repBA has to be activated by the formation of a pseudoknot immediately upstream of the repA Shine-Dalgarno sequence. A small antisense RNA, RNAI, controls replication of pMU720 by interacting with repBA mRNA to inhibit expression of repA both directly, by preventing formation of the pseudoknot, and indirectly, by inhibiting translation of repB. The mechanism of translational coupling in repBA was investigated using the specialized ribosome system, which directs a subpopulation of ribosomes that carry an altered anti-Shine-Dalgarno sequence to translate mRNA molecules whose Shine-Dalgarno sequences have been altered to be complementary to the mutant anti-Shine-Dalgarno sequence. Our data indicate that translation of repA involves reinitiation by the ribosome that has terminated translation of repB. The role of the pseudoknot in this process and its effect on the control of copy number in pMU720 are discussed.


Author(s):  
He Zhang ◽  
Xingxing Han ◽  
Zhaosong Wang ◽  
Zhiyong Wang ◽  
Yanfen Cui ◽  
...  

ATP-binding cassette (ABC) transporter family are major contributors to the drug resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells in vitro and in vivo. RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.


2011 ◽  
Vol 40 (7) ◽  
pp. 3152-3158 ◽  
Author(s):  
Yuka Adachi ◽  
Hiroshi Kuroda ◽  
Yasushi Yukawa ◽  
Masahiro Sugiura

2000 ◽  
Vol 19 (14) ◽  
pp. 3788-3798 ◽  
Author(s):  
Yoshio Inokuchi ◽  
Akikazu Hirashima ◽  
Yasuhiko Sekine ◽  
Laszlo Janosi ◽  
Akira Kaji

PLoS Biology ◽  
2009 ◽  
Vol 7 (8) ◽  
pp. e1000171 ◽  
Author(s):  
Linda Løvdok ◽  
Kajetan Bentele ◽  
Nikita Vladimirov ◽  
Anette Müller ◽  
Ferencz S. Pop ◽  
...  

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Yoshio Inokuchi ◽  
Fabio Quaglia ◽  
Hideko Kaji ◽  
Akira Kaji

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.


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