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• W2898872246 abstract "Calreticulin (CALR) is an endoplasmic reticulum (ER) protein that plays an important role as a calcium (Ca2+) buffering chaperone. Mutations in CALR exon 9 have been identified in essential thrombocythemia and primary myelofibrosis, two myeloproliferative neoplasms (MPNs) characterised by megakaryocyte hyperplasia. Despite the large body of research built around CALR mutations, many aspects of the oncogenic mechanisms of CALR in MPNs remain unanswered. This investigation aims to investigate whether CALR mutations affect the nature of the C-terminal domain of this protein, its sub-cellular compartmentalisation and its Ca2+ buffering activity during megakaryocyte hyperplasia. Additionally, this study establishes a new cellular model to investigate megakaryocyte differentiation in presence of CALR mutations. In silico analysis of the structural characteristics of CALR mutant C-terminal domain revealed that CALR mutations lead to changes in its secondary structure, its protein binding properties and changes the acidity of CALR mutant´s C-terminal domain. These physical alterations could affect CALR cellular behaviour by leading to inefficient ER Ca2+ buffering activity and lead to a novel oncogenic network of protein interactions. This study revealed that MARIMO leukemic cell line, which harbours a CALR mutation, has in vitro megakaryocyte differentiation potential. Importantly, this discovery was useful for further studies aiming to analyse CALR mutant cells during megakaryocyte commitment. Moreover, study of CALR mutant cellular localisation showed that this protein is localised within the ER, but it is also mislocalised within the cytoplasm and cell membrane, where it co-localised with thrombopoietin receptor. Interestingly, CALR cell surface expression increased during megakaryocyte commitment in CALR mutant cells, showing a dynamic process of CALR compartmentalisation during megakaryocyte differentiation. One of the more significant findings shown in this study is the emergence of intracellular Ca2+ concentrations ([Ca2+I]) as an important element during megakaryopoiesis. Importantly, CALR mutations impaired the cellular ER Ca2+ buffering activity and led to changes in the [Ca2+I] during the process of megakaryocyte differentiation. In addition, initial experimentsrevealed that physical manipulation of [Ca2+I] leads to the emergence of a megakaryocyte phenotype in leukemic cells, showing the relevance of this factor during megakaryocyte commitment. All together, these findings elucidate novel effects of CALR mutations into the physical and functional characteristics of CALR mutant in MPNs, describing new aspects of this driver mutation during the oncogenesis of these diseases. Finally, the current data highlight the importance of studying the effects of CALR mutations during the process of megakaryocyte differentiation, as CALR mutant sub-cellular compartmentalisation and ER Ca2+ buffering activity variate during the process of megakaryopoiesis." @default.
• W2898872246 created "2018-11-09" @default.
• W2898872246 creator A5067938397 @default.
• W2898872246 date "2018-06-29" @default.
• W2898872246 modified "2023-09-26" @default.
• W2898872246 title "New molecular and cellular aspects of mutant calreticulin in Myeloproliferative Neoplasms" @default.
• W2898872246 cites W130020229 @default.
• W2898872246 cites W1421162947 @default.
• W2898872246 cites W14748109 @default.
• W2898872246 cites W1480735239 @default.
• W2898872246 cites W1485297825 @default.
• W2898872246 cites W1503482160 @default.
• W2898872246 cites W1518642595 @default.
• W2898872246 cites W1529082289 @default.
• W2898872246 cites W1535599521 @default.
• W2898872246 cites W1551219357 @default.
• W2898872246 cites W1570226646 @default.
• W2898872246 cites W1586011497 @default.
• W2898872246 cites W1593385535 @default.
• W2898872246 cites W1599277155 @default.
• W2898872246 cites W1600052472 @default.
• W2898872246 cites W1650401181 @default.
• W2898872246 cites W1773256867 @default.
• W2898872246 cites W179120284 @default.
• W2898872246 cites W1832569329 @default.
• W2898872246 cites W1836124358 @default.
• W2898872246 cites W1848220733 @default.
• W2898872246 cites W1861594661 @default.
• W2898872246 cites W190906149 @default.
• W2898872246 cites W1958567900 @default.
• W2898872246 cites W1963736125 @default.
• W2898872246 cites W1963772181 @default.
• W2898872246 cites W1967467568 @default.
• W2898872246 cites W1967658150 @default.
• W2898872246 cites W1968410172 @default.
• W2898872246 cites W1968659980 @default.
• W2898872246 cites W1972001907 @default.
• W2898872246 cites W1973494414 @default.
• W2898872246 cites W1973752800 @default.
• W2898872246 cites W1975459052 @default.
• W2898872246 cites W1977287641 @default.
• W2898872246 cites W1977549744 @default.
• W2898872246 cites W1978564046 @default.
• W2898872246 cites W1980568348 @default.
• W2898872246 cites W1980633311 @default.
• W2898872246 cites W1983412285 @default.
• W2898872246 cites W1985177017 @default.
• W2898872246 cites W1986834666 @default.
• W2898872246 cites W1987134040 @default.
• W2898872246 cites W1987786553 @default.
• W2898872246 cites W1991274147 @default.
• W2898872246 cites W1991816411 @default.
• W2898872246 cites W1992041375 @default.
• W2898872246 cites W1992604276 @default.
• W2898872246 cites W1994840640 @default.
• W2898872246 cites W1995275861 @default.
• W2898872246 cites W1995782709 @default.
• W2898872246 cites W1998541114 @default.
• W2898872246 cites W1999274448 @default.
• W2898872246 cites W1999310504 @default.
• W2898872246 cites W2000598040 @default.
• W2898872246 cites W2000630388 @default.
• W2898872246 cites W2001414523 @default.
• W2898872246 cites W2002998283 @default.
• W2898872246 cites W2003274125 @default.
• W2898872246 cites W2003656981 @default.
• W2898872246 cites W2004234324 @default.
• W2898872246 cites W2004816473 @default.
• W2898872246 cites W2006216368 @default.
• W2898872246 cites W2008970948 @default.
• W2898872246 cites W2009860993 @default.
• W2898872246 cites W2010722071 @default.
• W2898872246 cites W2011722739 @default.
• W2898872246 cites W2011921884 @default.
• W2898872246 cites W2012703960 @default.
• W2898872246 cites W2016170088 @default.
• W2898872246 cites W2016612145 @default.
• W2898872246 cites W2017089028 @default.
• W2898872246 cites W2018983791 @default.
• W2898872246 cites W2019789856 @default.
• W2898872246 cites W2019889005 @default.
• W2898872246 cites W2020006960 @default.
• W2898872246 cites W2020426144 @default.
• W2898872246 cites W2020980799 @default.
• W2898872246 cites W2021796006 @default.
• W2898872246 cites W2028290171 @default.
• W2898872246 cites W2028674462 @default.
• W2898872246 cites W2029520051 @default.
• W2898872246 cites W2033164539 @default.
• W2898872246 cites W2033405819 @default.
• W2898872246 cites W2033620247 @default.
• W2898872246 cites W2036223010 @default.
• W2898872246 cites W2043427864 @default.
• W2898872246 cites W2043529047 @default.
• W2898872246 cites W2044296969 @default.
• W2898872246 cites W2044591804 @default.
• W2898872246 cites W2044730187 @default.
• W2898872246 cites W2048384162 @default.
• W2898872246 cites W2049145190 @default.
• W2898872246 cites W2053820259 @default.

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