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Full-Text Articles in Molecular Biology

Changes In Alternative Splicing As Pharmacodynamic Markers For Sudemycin D6, Morgan Thurman, Jacob Van Doorn, Barbara Danzer, Thomas R. Webb, Stefan Stamm Sep 2017

Changes In Alternative Splicing As Pharmacodynamic Markers For Sudemycin D6, Morgan Thurman, Jacob Van Doorn, Barbara Danzer, Thomas R. Webb, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

Objective:

The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood.

Methods:

Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction.

Results:

Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells.

Conclusions:

Exon skipping in the DUSP11 and SRRM1 pre-mRNAs ...


Structures Of Eccb1 And Eccd1 From The Core Complex Of The Mycobacterial Esx-1 Type Vii Secretion System, Jonathan Mark Wagner, Sum Chan, Timothy J. Evans, Sara Kahng, Jennifer Kim, Mark A. Arbing, David Eisenberg, Konstantin V. Korotkov Feb 2016

Structures Of Eccb1 And Eccd1 From The Core Complex Of The Mycobacterial Esx-1 Type Vii Secretion System, Jonathan Mark Wagner, Sum Chan, Timothy J. Evans, Sara Kahng, Jennifer Kim, Mark A. Arbing, David Eisenberg, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Background: The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system.

Results: This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB1 and EccD1. The periplasmic domain of EccB1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure ...


Computational Design Of The Affinity And Specificity Of A Therapeutic T Cell Receptor, Brian G. Pierce, Lance M. Hellman, Moushumi Hossain, Nishant K. Singh, Craig W. Vander Kooi, Zhiping Weng, Brian M. Baker Feb 2014

Computational Design Of The Affinity And Specificity Of A Therapeutic T Cell Receptor, Brian G. Pierce, Lance M. Hellman, Moushumi Hossain, Nishant K. Singh, Craig W. Vander Kooi, Zhiping Weng, Brian M. Baker

Molecular and Cellular Biochemistry Faculty Publications

T cell receptors (TCRs) are key to antigen-specific immunity and are increasingly being explored as therapeutics, most visibly in cancer immunotherapy. As TCRs typically possess only low-to-moderate affinity for their peptide/MHC (pMHC) ligands, there is a recognized need to develop affinity-enhanced TCR variants. Previous in vitro engineering efforts have yielded remarkable improvements in TCR affinity, yet concerns exist about the maintenance of peptide specificity and the biological impacts of ultra-high affinity. As opposed to in vitro engineering, computational design can directly address these issues, in theory permitting the rational control of peptide specificity together with relatively controlled increments in ...


Valproic Acid Causes Proteasomal Degradation Of Dicer And Influences Mirna Expression, Zhaiyi Zhang, Paolo Convertini, Manli Shen, Xiu Xu, Frédéric Lemoine, Pierre De La Grange, Douglas A. Andres, Stefan Stamm Dec 2013

Valproic Acid Causes Proteasomal Degradation Of Dicer And Influences Mirna Expression, Zhaiyi Zhang, Paolo Convertini, Manli Shen, Xiu Xu, Frédéric Lemoine, Pierre De La Grange, Douglas A. Andres, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to ...