Morphologic Responses to a Murine Erythroblastosis Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;

Kirsten, W. H.; Mayer, Lívia

doi:10.1093/jnci/39.2.311

Cited by 73 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The virus was named Harvey-MSV (Murine Sarcoma Virus) and shown to be the result of the recombination between retroviral genomes and a cellular rat gene (named Harvey-RAS, Ha-RAS, the name coming from for rat sarcoma) that was responsible for the transforming ability of this virus [1]. Shortly after, a different mouse retrovirus was isolated with the ability to induce erythroblastosis and sarcomas after several passages in newborn W/Fu rats [2], and subsequent work also demonstrated a recombinational mechanism of origin for this new transforming retrovirus that involved, in this case, a different (but related) cellular rat gene (designated Kirsten-RAS, Ki-RAS) [3]. The same lab also made a number of important contributions to the characterization of these genes, including the discovery of mammalian cellular homologs of the viral RAS oncogenes [4] and the demonstration that these oncogenes were different from the paradigm src viral oncogene and coded for small proteins (21 kDa) able to bind guanine nucleotides [5].…”

Section: The Retroviral Ras Oncogenesmentioning

confidence: 99%

40 Years of RAS—A Historic Overview

Fernández‐Medarde

Rivas

Santos

2021

Genes

View full text Add to dashboard Cite

It has been over forty years since the isolation of the first human oncogene (HRAS), a crucial milestone in cancer research made possible through the combined efforts of a few selected research groups at the beginning of the 1980s. Those initial discoveries led to a quantitative leap in our understanding of cancer biology and set up the onset of the field of molecular oncology. The following four decades of RAS research have produced a huge pool of new knowledge about the RAS family of small GTPases, including how they regulate signaling pathways controlling many cellular physiological processes, or how oncogenic mutations trigger pathological conditions, including developmental syndromes or many cancer types. However, despite the extensive body of available basic knowledge, specific effective treatments for RAS-driven cancers are still lacking. Hopefully, recent advances involving the discovery of novel pockets on the RAS surface as well as highly specific small-molecule inhibitors able to block its interaction with effectors and/or activators may lead to the development of new, effective treatments for cancer. This review intends to provide a quick, summarized historical overview of the main milestones in RAS research spanning from the initial discovery of the viral RAS oncogenes in rodent tumors to the latest attempts at targeting RAS oncogenes in various human cancers.

show abstract

Section: The Retroviral Ras Oncogenesmentioning

confidence: 99%

40 Years of RAS—A Historic Overview

Fernández‐Medarde

Rivas

Santos

2021

Genes

View full text Add to dashboard Cite

show abstract

“…This oncogenic viral genetic element inducing Rat Sarcoma was named H-Ras (Harvey Ras) [3]. Later, while serially passing Mouse Erythroblastosis virus (MEV) in Wister-Furth (W/Fu) rats, Kirsten identified another retrovirus carrying the Ras gene [4]. Initially named as a variant of Src (sarcoma), this gene was not only mutated in a diverse spectrum of cancers but also encoded a 21k Da protein that had crucial cellular roles in normal cells.…”

Section: The History Of Ras Isoforms-from Viral Oncogenes To Pivotal Cellular Genesmentioning

confidence: 99%

Ras Isoforms from Lab Benches to Lives—What Are We Missing and How Far Are We?

Nair

Kubatzky

Saha

2021

IJMS

View full text Add to dashboard Cite

The central protein in the oncogenic circuitry is the Ras GTPase that has been under intense scrutiny for the last four decades. From its discovery as a viral oncogene and its non–oncogenic contribution to crucial cellular functioning, an elaborate genetic, structural, and functional map of Ras is being created for its therapeutic targeting. Despite decades of research, there still exist lacunae in our understanding of Ras. The complexity of the Ras functioning is further exemplified by the fact that the three canonical Ras genes encode for four protein isoforms (H-Ras, K-Ras4A, K-Ras4B, and N-Ras). Contrary to the initial assessment that the H-, K-, and N-Ras isoforms are functionally similar, emerging data are uncovering crucial differences between them. These Ras isoforms exhibit not only cell–type and context-dependent functions but also activator and effector specificities on activation by the same receptor. Preferential localization of H-, K-, and N-Ras in different microdomains of the plasma membrane and cellular organelles like Golgi, endoplasmic reticulum, mitochondria, and endosome adds a new dimension to isoform-specific signaling and diverse functions. Herein, we review isoform-specific properties of Ras GTPase and highlight the importance of considering these towards generating effective isoform-specific therapies in the future.

show abstract

“…We further studied HRas as an important target that might mediate the effects of 15d-PGJ 2 on muscle differentiation via covalent modification. We investigated HRas as a possible effector of 15d-PGJ 2 because (i) HRas belongs to the Ras superfamily of small molecule GTPases and is known regulator of key cellular processes (BOHR Orthopredic Hospital et al, 1964 ;Davis et al, 1983 ;Kirsten and Mayer, 1967 ;Vetter and Wittinghofer, 2001 ). (ii) constitutively active HRas mutant (HRas V12) has been shown to inhibit the differentiation of myoblasts by inhibiting MyoD and Myogenin expression (Konieczny et al, 1989 ;Lassar et al, 1989 ;Olson,' et al, 1987;Van Der Burgt et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Senescent cells inhibit mouse myoblast differentiation via the SASP-lipid 15d-PGJ2 mediated modification and control of HRas

Pundlik,

Barik,

Venkateshvaran

et al. 2024

eLife

View full text Add to dashboard Cite

Senescent cells which are characterized by multiple features such as increased expression of SA β-gal and cell cycle inhibitors such as p21 or p16, accumulate with tissue damage and dysregulate tissue homeostasis. In the context of skeletal muscle, it is known that agents used for chemotherapy such as doxorubicin cause buildup of senescent cells, leading to the inhibition of tissue regeneration. Senescent cells influence neighboring cells via numerous secreted factors which form the senescence-associated secreted phenotype (SASP). Lipids are emerging as a key component of SASP that can control tissue homeostasis. Arachidonic acid-derived lipids have been shown to accumulate within senescent cells, specifically 15d-PGJ 2 , which is an electrophilic lipid produced by the non-enzymatic dehydration of the prostaglandin PGD 2 . In this study, we show that 15d-PGJ 2 is also released by Doxorubicin-induced senescent cells as a SASP factor. Treatment of skeletal muscle myoblasts with the conditioned medium from these senescent cells inhibits myoblast fusion during differentiation. Inhibition of L-PTGDS, the enzyme that synthesizes PGD 2 , diminishes the release of 15d-PGJ 2 by senescent cells and restores muscle differentiation. We further show that this lipid post-translationally modifies Cys184 of HRas in skeletal muscle cells, causing a reduction in the localization of HRas to the Golgi, increased HRas binding to RAF RBD, and activation of cellular MAPK-Erk signaling (but not the Akt signaling). Mutating C184 of HRas prevents the ability of 15d-PGJ 2 to inhibit the differentiation of muscle cells and control the activity of HRas. This work shows that 15d-PGJ 2 released from senescent cells could be targeted to restore muscle homeostasis after chemotherapy.

show abstract

Morphologic Responses to a Murine Erythroblastosis Virus<xref ref-type="fn" rid="FN1">2</xref>

Cited by 73 publications

References 0 publications

40 Years of RAS—A Historic Overview

40 Years of RAS—A Historic Overview

Ras Isoforms from Lab Benches to Lives—What Are We Missing and How Far Are We?

Senescent cells inhibit mouse myoblast differentiation via the SASP-lipid 15d-PGJ2 mediated modification and control of HRas

Contact Info

Product

Resources

About