The Essential Role of Protein Phosphatase-1 in Mitogenic Signaling and Breast Cancer

2001 ◽  
Author(s):  
Carey Oliver ◽  
Shirish Shenolikar
2004 ◽  
Vol 15 (10) ◽  
pp. 4395-4405 ◽  
Author(s):  
Natalia Vereshchagina ◽  
Daimark Bennett ◽  
Balázs Szöőr ◽  
Jasmin Kirchner ◽  
Sascha Gross ◽  
...  

Reversible phosphorylation of myosin regulatory light chain (MRLC) is a key regulatory mechanism controlling myosin activity and thus regulating the actin/myosin cytoskeleton. We show that Drosophila PP1β, a specific isoform of serine/threonine protein phosphatase 1 (PP1), regulates nonmuscle myosin and that this is the essential role of PP1β. Loss of PP1β leads to increased levels of phosphorylated nonmuscle MRLC (Sqh) and actin disorganisation; these phenotypes can be suppressed by reducing the amount of active myosin. Drosophila has two nonmuscle myosin targeting subunits, one of which (MYPT-75D) resembles MYPT3, binds specifically to PP1β, and activates PP1β's Sqh phosphatase activity. Expression of a mutant form of MYPT-75D that is unable to bind PP1 results in elevation of Sqh phosphorylation in vivo and leads to phenotypes that can also be suppressed by reducing the amount of active myosin. The similarity between fly and human PP1β and MYPT genes suggests this role may be conserved.


2020 ◽  
Vol 13 ◽  
Author(s):  
Andra Piciu ◽  
Alexandru Mester ◽  
George Rusu ◽  
Doina Piciu

Background: Thyroid carcinoma represents a complex pathology that can still be considered a medical challenge, despite having a better prognosis and life expectancy than most other neoplasms, also the scenario of multiple malignancies involving thyroid cancer is nowadays a common reality. Materials and methods: We reviewed the literature regarding the aggressive presentation of synchronous thyroid and breast cancer. In the current paper we are reporting the case of a 59 years-old woman, diagnosed with invasive ductal breast carcinoma and papillary thyroid carcinoma, presenting a natural history of both aggressive synchronous tumors. At the moment of hospitalization, the diagnostic was breast carcinoma with multiple secondary lesions, suggestive for lung and bone metastases, and nodular goiter. Results: Searching the literature PUBMED with the terms “thyroid carcinoma and synchronous breast carcinoma we found 86 studies; introducing the term “aggressive” the result included 4 studies, among them none being relevant for aggressive and synchronous. A similar search was done in SCOPUS finding 92 documents and after introducing the term aggressive, the number of papers was 8, none being for the synchronous aggressive metastatic thyroid and breast carcinoma. The majority of imaging diagnostic tools were used in this particular medical case, in order to ensure the best potential outcome. The final diagnostic was papillary thyroid carcinoma with lung and unusual multiple bone metastases and synchronous invasive ductal breast carcinoma with subcutaneous metastases. Conclusion: The case illustrates the challenges in correct assessment of oncologic patients, despite the advances in medical imaging and technologies and underlines the essential role of nuclear medicine procedures in the diagnostic and therapy protocols.


2018 ◽  
Vol 124 ◽  
pp. 108
Author(s):  
Katherina Alsina ◽  
Mohit Hulsurkar ◽  
Chunxia Yao ◽  
Barbara Langer ◽  
David Chiang ◽  
...  

2010 ◽  
Vol 426 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Jofre Ferrer-Dalmau ◽  
Asier González ◽  
Maria Platara ◽  
Clara Navarrete ◽  
José L. Martínez ◽  
...  

Maintenance of cation homoeostasis is a key process for any living organism. Specific mutations in Glc7, the essential catalytic subunit of yeast protein phosphatase 1, result in salt and alkaline pH sensitivity, suggesting a role for this protein in cation homoeostasis. We screened a collection of Glc7 regulatory subunit mutants for altered tolerance to diverse cations (sodium, lithium and calcium) and alkaline pH. Among 18 candidates, only deletion of REF2 (RNA end formation 2) yielded increased sensitivity to these conditions, as well as to diverse organic toxic cations. The Ref2F374A mutation, which renders it unable to bind Glc7, did not rescue the salt-related phenotypes of the ref2 strain, suggesting that Ref2 function in cation homoeostasis is mediated by Glc7. The ref2 deletion mutant displays a marked decrease in lithium efflux, which can be explained by the inability of these cells to fully induce the Na+-ATPase ENA1 gene. The effect of lack of Ref2 is additive to that of blockage of the calcineurin pathway and might disrupt multiple mechanisms controlling ENA1 expression. ref2 cells display a striking defect in vacuolar morphogenesis, which probably accounts for the increased calcium levels observed under standard growth conditions and the strong calcium sensitivity of this mutant. Remarkably, the evidence collected indicates that the role of Ref2 in cation homoeostasis may be unrelated to its previously identified function in the formation of mRNA via the APT (for associated with Pta1) complex.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Neha Nagpal ◽  
Shivani Sharma ◽  
Sourobh Maji ◽  
Giorgio Durante ◽  
Manuela Ferracin ◽  
...  

2018 ◽  
Vol 17 (4) ◽  
pp. 825-837 ◽  
Author(s):  
Sung Baek Jeong ◽  
Ji Hye Im ◽  
Jeong-Hoon Yoon ◽  
Quyen Thu Bui ◽  
Sung Chul Lim ◽  
...  

Cell Calcium ◽  
2014 ◽  
Vol 56 (4) ◽  
pp. 285-295 ◽  
Author(s):  
Elia Ranzato ◽  
Valeria Magnelli ◽  
Simona Martinotti ◽  
Zeina Waheed ◽  
Stuart M. Cain ◽  
...  

Open Biology ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 130138 ◽  
Author(s):  
Wei Theng Poh ◽  
Gaganmeet Singh Chadha ◽  
Peter J. Gillespie ◽  
Philipp Kaldis ◽  
J. Julian Blow

The initiation of DNA replication requires two protein kinases: cyclin-dependent kinase (Cdk) and Cdc7. Although S phase Cdk activity has been intensively studied, relatively little is known about how Cdc7 regulates progression through S phase. We have used a Cdc7 inhibitor, PHA-767491, to dissect the role of Cdc7 in Xenopus egg extracts. We show that hyperphosphorylation of mini-chromosome maintenance (MCM) proteins by Cdc7 is required for the initiation, but not for the elongation, of replication forks. Unlike Cdks, we demonstrate that Cdc7 executes its essential functions by phosphorylating MCM proteins at virtually all replication origins early in S phase and is not limiting for progression through the Xenopus replication timing programme. We demonstrate that protein phosphatase 1 (PP1) is recruited to chromatin and rapidly reverses Cdc7-mediated MCM hyperphosphorylation. Checkpoint kinases induced by DNA damage or replication inhibition promote the association of PP1 with chromatin and increase the rate of MCM dephosphorylation, thereby counteracting the previously completed Cdc7 functions and inhibiting replication initiation. This novel mechanism for regulating Cdc7 function provides an explanation for previous contradictory results concerning the control of Cdc7 by checkpoint kinases and has implications for the use of Cdc7 inhibitors as anti-cancer agents.


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