scholarly journals Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells

Author(s):  
Chihaya Maesawa
Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 733-742 ◽  
Author(s):  
C.V. Cabrera

A comparison of the patterns of expression of AS-C (T3) RNA and protein suggests that an important level of regulation occurs post-transcriptionally. First, when the RNA is abundant in the early embryo the protein is barely detectable. Later, the protein starts to accumulate in only a subset of the nuclei of those cells expressing the RNA. Only the cells in the subsets become the neuroblasts. This post-transcriptional regulation is suppressed in embryos mutant for the genes Notch and Delta; where all cells expressing RNA accumulate protein. These findings suggest that deployment of T3 protein expression is one of the causal factors that assigns specific fates to the neuroblasts and, in consequence, a basis for the mechanism of lateral inhibition is proposed.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8601-8601
Author(s):  
H. Ikeda ◽  
T. Hideshima ◽  
G. Perrone ◽  
Y. Okawa ◽  
N. Raje ◽  
...  

8601 Background: The mutations of P53 tumor suppressor protein are associated with progressive in Multiple Myeloma (MM), conversely, stabilization of P53 leads to cell cycle arrest and apoptosis. In this study, we examined p53 protein expression and demonstrated the effect of P53 stabilization using a novel specific P53 stabilizer CBS9106 in MM. Method: We examined P53 protein expression using Immunoblot analysis, as well as the growth inhibitory effect of CBS9106 in MM cell lines and primary tumor cells from MM patients. We also defined whether CBS9106 can overcome the growth promoting effect of exogenous cytokines and bone marrow stroma cells (BMSCs) using [3H]-thymidine uptake assay. Results: Expression of P53 protein was observed in 3/3 primary tumor cells from MM patients and 6/6 MM cell lines. CBS9106 at low nM levels triggered cytotoxicity against p53 wild type MM cell lines and primary tumor cells from MM patients, associated with phosphorylation of P53 (serine15 and 20). In contrast, CBS9106 did not affect the survival of normal peripheral blood mononuclear cells from healthy volunteers at concentrations as high as 10 μM. This agent also induced G1 cell cycle arrest, followed by apoptosis associated with cleavage of caspase-3, -8, -9 and PARP. Neither growth stimulating cytokines (IL-6 and IGF-1) nor BMSCs protected against apoptotic effect of CBS9106. Moreover, we demonstrate that combination of CBS9106 with MDM2 inhibitor Nutrin3 or proteasome inhibitor bortezomib induces synergistic anti-MM activity in both P53 wild type MM cell lines and primary tumor cells from MM patients. Conclusions: Stabilizing P53 by CBS9106 represents a novel promising p53-based therapy in MM. These results provide the preclinical framework supporting evaluation of CBS9106 in clinical trials to improve patient outcome in MM. No significant financial relationships to disclose.


FEBS Letters ◽  
2003 ◽  
Vol 544 (1-3) ◽  
pp. 218-222 ◽  
Author(s):  
Ling Gu ◽  
Haoqiang Ying ◽  
Hongwu Zheng ◽  
Stephen A. Murray ◽  
Zhi-Xiong Jim Xiao

2017 ◽  
Vol 26 (14) ◽  
pp. 2732-2746 ◽  
Author(s):  
Francesca Svetoni ◽  
Elisa De Paola ◽  
Piergiorgio La Rosa ◽  
Neri Mercatelli ◽  
Daniela Caporossi ◽  
...  

2020 ◽  
Author(s):  
Pearl V. Ryder ◽  
Junnan Fang ◽  
Dorothy A. Lerit

AbstractCentrosomes are microtubule-organizing centers required for error-free mitosis and embryonic development. The microtubule-nucleating activity of centrosomes is conferred by the pericentriolar material (PCM), a composite of numerous proteins subject to cell cycle-dependent oscillations in levels and organization. In diverse cell types, mRNAs localize to centrosomes and may contribute to changes in PCM abundance. Here, we investigate the regulation of mRNA localization to centrosomes in the rapidly cycling Drosophila melanogaster embryo. We find that RNA localization to centrosomes is regulated during the cell cycle and developmentally. We identify a novel role for the fragile-X mental retardation protein (FMRP), which localizes to pericentrosomal RNA granules, in the post-transcriptional regulation of centrosomal RNA. Further, the mis-targeting of a model centrosomal mRNA, centrocortin (cen), is sufficient to alter cognate protein localization to centrosomes and impair spindle morphogenesis and genome stability.


2002 ◽  
Vol 278 (5) ◽  
pp. 2947-2955 ◽  
Author(s):  
Olivia Crociani ◽  
Leonardo Guasti ◽  
Manuela Balzi ◽  
Andrea Becchetti ◽  
Enzo Wanke ◽  
...  

Development ◽  
1989 ◽  
Vol 106 (1) ◽  
pp. 95-103 ◽  
Author(s):  
T.L. Karr ◽  
T.B. Kornberg

The fushi tarazu (ftz) gene is essential for segmentation of the Drosophila embryo. This requirement is reflected at the cellular blastoderm stage of embryogenesis by seven transverse stripes of ftz expression. These stripes correspond to the missing segments of ftz mutant embryos. We describe here novel intermediate patterns of ftz protein expression which were detected in younger embryos by using anti-ftz antibodies and a sensitive fluorescence/immunoperoxidase technique (‘filtered fluorescence imaging’, FFI). Striped patterns of ftz protein evolved continuously, and the different stripes appeared in an ordered sequence, involving both anterior-posterior (A/P) and dorsal-ventral (D/V) progressions. Comparison of these patterns of ftz protein with those of ftz RNA suggests that these novel aspects of the patterning process involve post-transcriptional regulation in addition to the transcriptional control known to be involved in expression of this gene.


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