scholarly journals Negative regulation of cell-cycle progression by RINGO/Speedy E

2008 ◽  
Vol 410 (3) ◽  
pp. 535-542 ◽  
Author(s):  
Ana Dinarina ◽  
E. Josué Ruiz ◽  
Ana O'loghlen ◽  
Silvana Mouron ◽  
Laurent Perez ◽  
...  

Cell-cycle transitions are controlled by CDKs (cyclin-dependent kinases), whose activation is usually associated with the binding of cyclins. RINGO/Speedy proteins can also bind to and activate CDKs, although they do not have amino acid sequence homology with cyclins. The RINGO/Speedy family members studied so far positively regulate cell-cycle progression. In the present paper, we report the biochemical and functional characterization of RINGO/Speedy E. We show that RINGO/Speedy E is a functionally distant member of this protein family that negatively affects cell-cycle progression. RINGO/Speedy E overexpression inhibits the meiotic progression in Xenopus oocytes as well as the proliferation of mammalian cells. RINGO/Speedy E can bind to endogenous CDK1 and CDK2 in both cellular systems. However, the RINGO/Speedy E-activated CDKs have different substrate specificity than the CDKs activated by other RINGO/Speedy proteins, which may account for their different effects on the cell cycle. Our results indicate that, although all RINGO/Speedy family members can activate CDKs, they may differently regulate cell-cycle progression.

2000 ◽  
Vol 113 (10) ◽  
pp. 1687-1694 ◽  
Author(s):  
F. Reymond ◽  
C. Wirbelauer ◽  
W. Krek

Present in organisms ranging from yeast to man, homologues of the Saccharomyces cerevisiae ubiquitin-conjugating enzyme CDC34 have been shown to play important roles in the regulation of cell cycle progression and checkpoint function. Here we analyze the expression and intracellular localization of endogenous CDC34 during mammalian cell cycle progression. We find that CDC34 protein is constitutively expressed during all stages of the cell cycle. Immunofluorescence experiments reveal that during interphase, endogenous CDC34 is localized to distinct speckles in both the nucleus and the cytoplasm. The presence of CDC34 in these compartments has also been established by biochemical fractionation experiments. Interestingly, nuclear localization depends on the presence of specific carboxy-terminal CDC34 sequences that have previously been shown to be required for CDC34's cell cycle function in Saccharomyces cerevisiae. Finally, we find that in anaphase and not during early stages of mitosis, CDC34 colocalizes with (beta)-tubulin at the mitotic spindle, implying that it may contribute to spindle function at later stages of mitosis. Taken together, these results support a model in which CDC34 ubiquitin-conjugating enzyme functions in the regulation of nuclear and cytoplasmic activities as well as in the process of chromosome segregation at the onset of anaphase in mammalian cells.


2020 ◽  
Vol 10 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Hamed Shoorei ◽  
Farhad Tondro Anamag ◽  
Mohammad Taheri

Cell cycle is regulated by a number of proteins namely cyclin-dependent kinases (CDKs) and their associated cyclins which bind with and activate CDKs in a phase specific manner. Additionally, several transcription factors (TFs) such as E2F and p53 and numerous signaling pathways regulate cell cycle progression. Recent studies have accentuated the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of cell cycle. Both lncRNAs and miRNAs interact with TFs participating in the regulation of cell cycle transition. Dysregulation of cell cycle regulatory miRNAs and lncRNAs results in human disorders particularly cancers. Understanding the role of lncRNAs, miRNAs, and TFs in the regulation of cell cycle would pave the way for design of anticancer therapies which intervene with the cell cycle progression. In the current review, we describe the role of lncRNAs and miRNAs in the regulation of cell cycle and their association with human malignancies.


2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.


2001 ◽  
pp. 220-227
Author(s):  
Owen W. J. Prall ◽  
Eileen M. Rogan ◽  
Elizabeth A. Musgrove ◽  
Colin K. W. Watts ◽  
Robert L. Sutherland

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