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41.
Multiple myeloma (MM) is a complex disease driven by numerous genetic and epigenetic alterations that are acquired over time. Despite recent progress in the understanding of MM pathobiology and the availability of innovative drugs, which have pronounced clinical outcome, this malignancy eventually progresses to a drug-resistant lethal stage and, thus, novel therapeutic drugs/models always play an important role in effective management of MM. Modulation of tumor microenvironment is one of the hallmarks of cancer biology, including MM, which affects the myeloma genomic architecture and disease progression subtly through chromatin modifications. The bone marrow niche has a prime role in progression, survival, and drug resistance of multiple myeloma cells. Therefore, it is important to develop means for targeting the ecosystem between multiple myeloma bone marrow microenvironment and chromatin remodeling. Extensive gene expression profile analysis has indeed provided the framework for new risk stratification of MM patients and identifying novel molecular targets and therapeutics. However, key tumor microenvironment factors/immune cells and their interactions with chromatin remodeling complex proteins that drive MM cell growth and progression remain grossly undefined. 相似文献
42.
Jing Chen Gang Li Chao Wan Yixuan Li Lianci Peng Rendong Fang Yuanyi Peng Chao Ye 《Viruses》2022,14(7)
Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected pigs. Latent infected pigs can then serve as the source of recurrent infection, which is one of the difficulties for PRV eradication. Virus latency refers to the retention of viral complete genomes without production of infectious progeny virus; however, following stress stimulus, the virus can be reactivated into lytic infection, which is known as the latency-reactivation cycle. Recently, several research have indicated that alphaherpesvirus latency and reactivation is regulated by a complex interplay between virus, neurons, and the immune system. However, with those limited reports, the relevant advances in PRV latency are lagging behind. Therefore, in this review we focus on the regulatory mechanisms in PRV latency via summarizing the progress of PRV itself and that of other alphaherpesviruses, which will improve our understanding in the underlying mechanism of PRV latency and help design novel therapeutic strategies to control PRV latency. 相似文献
43.
As in monotreme mammals, the pectoral apparatus of basal (fossil) amniotes includes two coracoid elements, the procoracoid and metacoracoid. Among extant reptiles the metacoracoid has long been assumed lost; this notion is herein challenged. A comprehensive review of data from numerous sources, including the fossil record, experimental embryology, genetic manipulations and an analysis of morphology at the level cell condensations, supports the conclusion that the metacoracoid gives rise to the majority of the reptilian coracoid. By contrast, the reptilian procoracoid remains as a rudiment that is incorporated as a process of the (meta)coracoid and/or the glenoid region of the scapula early during development, prior to skeletogenesis. Application of this integrated approach corroborates and enhances previous work describing the evolution of the pectoral apparatus in mammals. A revised scenario of amniote coracoid evolution is presented emphasizing the importance of considering cell condensations when evaluating the homology of a skeletal complex. 相似文献
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Centrosomes, major regulatory sites for the microtubule (MT) nucleation, are regulated in a dynamic manner throughout the process of meiotic maturation. Recently, centrosome orientation in mouse oocytes has been demonstrated in metaphase I through metaphase II. However, centrosomal protein expression in concordance with MT polymerization in earlier stages of oocyte maturation from germinal vesicle stage (GV) to prometaphase I still remains unclear. The present study aims to assess the centrosome-microtubule remodelling during the onset of meiosis based on strict criteria of nuclear maturation. Six consecutive stages were determined for scoring the oocytes as unrimmed nucleolus (UR), partially rimmed nucleolus (PR), fully rimmed nucleolus (FR), nuclear lamina dissolution (NLD), disappearance of nucleolus (DON), and chromatin condensation (CC). A centrosomal protein, pericentrin, was found tightly localized adjacent to nuclear lamina in UR, lacking any MT nucleation activity. In concordance with the competency to resume meiosis, an increase in the amount and nucleation capacity of pericentrin is noted. In FR, cytoplasmic MT almost disappeared while de-novo microtubule polymerization was found in small aggregates of pericentrin localized around the nucleus. Towards the end of DON and CC, a sudden burst of pericentrin was noted with an extreme MT nucleation activity in an organized fashion that is essential for the rapid formation of first meiotic spindle. The results show that centrosomes display precisely controlled spatio-temporal changes during the onset of meiotic maturation. Accumulation of centrosomal proteins to a single locus followed by a sequestration to several spots might be evidence of a mechanism by which the proper distribution of centrosomal material during nuclear breakdown and subsequently formation of spindle are regulated in concordance with the nuclear maturation. 相似文献
49.
All cells that constitute mature tissues in an eukaryotic organism undergo a multistep process of cell differentiation. At
the terminal stage of this process, cells either cease to proliferate forever or rest for a very long period of time. During
terminal differentiation, most of the genes that are required for cell ‘housekeeping’ functions, such as proto-oncogenes and
other cell-cycle and cell proliferation genes, become stably repressed. At the same time, nuclear chromatin undergoes dramatic
morphological and structural changes at the higher-order levels of chromatin organization. These changes involve both constitutively
inactive chromosomal regions (constitutive heterochromatin) and the formerly active genes that become silenced and structurally
modified to form facultative heterochromatin. Here we approach terminal cell differentiation as a unique system that allows
us to combine biochemical, ultrastructural and molecular genetic techniques to study the relationship between the hierarchy
of chromatin higher-order structures in the nucleus and its function(s) in dynamic packing of genetic material in a form that
remains amenable to regulation of gene activity and other DNA-dependent cellular processes. 相似文献
50.
Jim Jinn‐Chyuan Sheu Jung Hye Choi Bin Guan Fuu‐Jen Tsai Chun‐Hung Hua Ming‐Tsung Lai Tian‐Li Wang Ie‐Ming Shih 《The Journal of pathology》2013,229(4):559-568
Chromosome 11q13.5 containing RSF1 (HBXAP), a gene involved in chromatin remodelling, is amplified in several human cancers including ovarian carcinoma. Our previous studies demonstrated requirement of Rsf‐1 for cell survival in cancer cells, which contributed to tumour progression; however, its role in tumourigenesis has not yet been elucidated. In this study, we co‐immunoprecipitated proteins with Rsf‐1 followed by nanoelectrospray mass spectrometry and identified cyclin E1, besides SNF2H, as one of the major Rsf‐1 interacting proteins. Like RSF1, CCNE1 is frequently amplified in ovarian cancer, and both Rsf‐1 and cyclin E1 were found co‐up‐regulated in ovarian cancer tissues. Ectopic expression of Rsf‐1 and cyclin E1 in non‐tumourigenic TP53mut RK3E cells led to an increase in cellular proliferation and tumour formation by activating cyclin E1‐associated kinase (CDK2). Tumourigenesis was not detected if either cyclin E1 or Rsf‐1 was expressed, or they were expressed in a TP53wt background. Domain mapping showed that cyclin E1 interacted with the first 441 amino acids of Rsf‐1. Ectopic expression of this truncated domain significantly suppressed G1/S‐phase transition, cellular proliferation, and tumour formation of RK3E‐p53R175H/Rsf‐1/cyclin E1 cells. The above findings suggest that Rsf‐1 interacts and collaborates with cyclin E1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour‐promoting functions of the RSF/cyclin E1 complex. 相似文献