WorldCat Identities

Rajalingam, Krishnaraj

Overview
Works: 20 works in 21 publications in 1 language and 54 library holdings
Roles: dgs, Contributor, Author, Other
Publication Timeline
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Most widely held works by Krishnaraj Rajalingam
Novel role for ARAF kinase in regulating MAPK signaling and cancer by Juliane Mooz( )

1 edition published in 2015 in English and held by 11 WorldCat member libraries worldwide

The RAF family of kinases constitutes the members A, B and CRAF. They mediate RAS signaling by linking it to the MEK/ERK transduction module, which regulates cellular processes such as cell proliferation, migration, survival and cell death. As the RAS/RAF/MEK/ERK (MAPK) pathway is found to be activated in human cancers, the RAF kinases have been exploited as valuable therapeutic targets and RAF inhibitors show promising results in the clinic, esp. with tumors harboring an activating BRAFV600E mutation. However, RAF inhibitors paradoxically accelerate metastasis in RAS mutant and BRAF wildtype tumors. They also become ineffective over time in BRAFV600E tumors because of reactivation of downstream mitogen-activated protein kinase (MAPK) signaling by promoting RAF dimerization. Aims of the present work were 1) to investigate the role of ARAF kinase in the paradoxical activation of the enzymatic cascade by RAF inhibitors downstream of mutated RAS and 2) to study the consequences of the loss of ARAF function on signal transduction in vitro and in vivo (nude mice). We have engineered several cell lines that would allow the study of basal and RAF inhibitor induced effects on MAPK activation, tumor cell migration and invasion. In summary, we were able to show that the RAF isoform ARAF has an obligatory role in promoting MAPK activity and tumor cell invasion in a cell type dependent manner. In these cell types, ARAF depletion prevented the activation of MAPK kinase 1 (MEK1) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and led to a significant decrease of protrusions growing out of tumor cell spheroids in a three-dimensional (3D) culture that were otherwise induced by BRAFV600E-specific or BRAF/CRAF inhibitors (GDC-0879 and sorafenib, respectively). RAF inhibitors stimulated homodimerization of ARAF and heteromerization of BRAF with CRAF and the scaffolding protein KSR1. However, induced oligomerization was not sufficient to activate MAPK signaling if ARAF was depleted. By employing full length recombinant kinases, we were able to show for the first time that the three RAF isoforms competed for the binding to MEK1. In cell culture models, the overexpression of dimer-deficient ARAF mutants impaired the interaction between ARAF and endogenous MEK1 and thus prevented the subsequent phosphorylation of MEK1 and ERK1/2. Our findings reveal a new role for ARAF in directly activating the MAPK cascade through homodimerization and thereby promoting tumor cell invasion, suggesting the conserved RAF-dimer interface as a target for RAS- and RAF mediated cancer therapy. Collectively, we provide evidence for the dual role ARAF plays in controlling MAPK signaling and cancer as loss of ARAF promoted strong lung metastasis formation in nude mice. Preliminary data describing the underlying mechanisms behind ARAF-regulated metastases have been presented and discussed
Modulation of apoptosis by Chlamydophila pneumoniae infection and caspase mediated cleavage of c-Abl and PKG by Krishnaraj Rajalingam( Book )

2 editions published between 2003 and 2004 in English and held by 7 WorldCat member libraries worldwide

ERK3/MAPK6 controls IL-8 production and chemotaxis by Katarzyna Bogucka( )

1 edition published in 2020 in English and held by 3 WorldCat member libraries worldwide

Abstract: ERK3 is a ubiquitously expressed member of the atypical mitogen activated protein kinases (MAPKs) and the physiological significance of its short half-life remains unclear. By employing gastrointestinal 3D organoids, we detect that ERK3 protein levels steadily decrease during epithelial differentiation. ERK3 is not required for 3D growth of human gastric epithelium. However, ERK3 is stabilized and activated in tumorigenic cells, but deteriorates over time in primary cells in response to lipopolysaccharide (LPS). ERK3 is necessary for production of several cellular factors including interleukin-8 (IL-8), in both, normal and tumorigenic cells. Particularly, ERK3 is critical for AP-1 signaling through its interaction and regulation of c-Jun protein. The secretome of ERK3-deficient cells is defective in chemotaxis of neutrophils and monocytes both in vitro and in vivo. Further, knockdown of ERK3 reduces metastatic potential of invasive breast cancer cells. We unveil an ERK3-mediated regulation of IL-8 and epithelial secretome for chemotaxis
Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis by Vera Kozjak-Pavlovic( )

1 edition published in 2011 in English and held by 2 WorldCat member libraries worldwide

IAPs as E3 ligases of Rac1 : shaping the move by Tripat Kaur Oberoi-Khanuja( )

1 edition published in 2012 in English and held by 2 WorldCat member libraries worldwide

Ubiquitylation in immune disorders and cancer: from molecular mechanisms to therapeutic implications by Simone Fulda( )

1 edition published in 2012 in English and held by 2 WorldCat member libraries worldwide

Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells( )

1 edition published in 2008 in English and held by 2 WorldCat member libraries worldwide

Attenuation of the ELAV1-like protein HuR sensitizes adenocarcinoma cells to the intrinsic apoptotic pathway by increasing the translation of caspase-2L by Christoph Winkler( )

1 edition published in 2016 in English and held by 2 WorldCat member libraries worldwide

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1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

The Myb-related protein MYPOP is a novel intrinsic host restriction factor of oncogenic human papillomaviruses by Elena Wüstenhagen( )

1 edition published in 2018 in English and held by 2 WorldCat member libraries worldwide

Role for caspase-2 during pore-forming toxin-mediated apoptosis by Imre Gergely( )

1 edition published in 2012 in English and held by 2 WorldCat member libraries worldwide

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1 edition published in 2013 in English and held by 2 WorldCat member libraries worldwide

IAPs on the move : role of inhibitors of apoptosis proteins in cell migration by Tripat Kaur Oberoi-Khanuja( )

1 edition published in 2013 in English and held by 2 WorldCat member libraries worldwide

IAP-IAP complexes required for apoptosis resistance of C. trachomatis-infected cells( )

1 edition published in 2006 in English and held by 2 WorldCat member libraries worldwide

The C-terminus of p63 contains multiple regulatory elements with different functions by Wesley E Straub( )

1 edition published in 2010 in English and held by 2 WorldCat member libraries worldwide

Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV pili( )

1 edition published in 2009 in English and held by 2 WorldCat member libraries worldwide

Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases by Dong Wang( )

1 edition published in 2020 in English and held by 2 WorldCat member libraries worldwide

Ubiquitin-dependent regulation of Cdc42 by XIAP by Arun Murali( )

1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection by Oliver Kepp( )

1 edition published in 2009 in English and held by 2 WorldCat member libraries worldwide

Apoptosis inhibitor 5: Role in the inhibition of caspase-2( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

 
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Audience Level
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Audience level: 0.96 (from 0.88 for Apoptosis ... to 0.97 for Modulation ...)

Alternative Names
Krishnaraj Rajalingam wetenschapper

Languages
English (21)