The ribonuclease/angiogenin inhibitor is also present in mitochondria and nuclei

Furia, Adriana; Moscato, Marco; Calı̀, Gaetano; Pizzo, Elio; Confalone, Elena; Amoroso, Maria Rosaria; Esposito, Franca; Nitsch, Lucio; D’Alessio, Giuseppe

doi:10.1016/j.febslet.2011.01.034

Cited by 31 publications

(29 citation statements)

References 23 publications

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“…There are several conflicting reports about the role of RNH1. For example, siRNA knockdown of RNH1 does not sensitize cells to noncytotoxic RNases, and its role in oxidative damage is not firmly established (7,8,12,13). However, despite these observations, the physiological functions of RNH1 remain unexplored.…”

Section: Introductionmentioning

confidence: 98%

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Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation

Chennupati¹,

Veiga²,

Maslowski³

et al. 2018

Journal of Clinical Investigation

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Section: Introductionmentioning

confidence: 98%

“…It is mainly localized in the cytosol, but can also be found in the nucleus and mitochondria (8). RNH1 was the first LRR protein to be crystallized, revealing a horseshoe-shaped 3D structure (9).…”

Section: Introductionmentioning

confidence: 99%

Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation

Chennupati¹,

Veiga²,

Maslowski³

et al. 2018

Journal of Clinical Investigation

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“…A surprising finding is that RNH1 was found to be mainly located in the nucleus under growth conditions. RNH1 was previously considered to be a cytoplasmic protein (Haigis et al, 2003) even though it had also been detected in the nucleus (Furia et al, 2011). The role of nuclear RNH1 under growth conditions is currently unclear.…”

Section: Dynamic Cellular Localization Of Ang and Rnh1mentioning

confidence: 99%

“…Therefore, the ribonucleolytic activity of ANG is essential, and an important question is how ANG avoids the surveillance action of RNH1 that is abundant (Haigis et al, 2003) in both cytoplasm and nucleus (Furia et al, 2011) and that binds ANG with femtomolar affinity (Lee et al, 1989). To address this question, we first examined the protein levels of ANG and RNH1 in the cytoplasm and nucleus of HeLa cells under growth and stress conditions.…”

Section: Differential Subcellular Localization Of Ang and Rnh1 Under mentioning

confidence: 99%

Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

Pizzo

Sarcinelli

Sheng

et al. 2013

Journal of Cell Science

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102

114

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SummaryAngiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription. When cells are stressed, ANG mediates the production of tRNA-derived stressinduced small RNA (tiRNA), which reprograms protein translation into a survival mechanism. The ribonucleolytic activity of ANG is essential for both processes but how this activity is regulated is unknown. We report here that ribonuclease/angiogenin inhibitor 1 (RNH1) controls both the localization and activity of ANG. Under growth conditions, ANG is located in the nucleus and is not associated with RNH1 so that the ribonucleolytic activity is retained to ensure rRNA transcription. Cytoplasmic ANG is associated with and inhibited by RNH1 so that random cleavage of cellular RNA is prevented. Under stress conditions, ANG is localized to the cytoplasm and is concentrated in stress granules where it is not associated with RNH1 and thus remains enzymatically active for tiRNA production. By contrast, nuclear ANG is associated with RNH1 in stressed cells to ensure that the enzymatic activity is inhibited and no unnecessary rRNA is produced to save anabolic energy. Knockdown of RNH1 abolished stress-induced relocalization of ANG and decreased cell growth and survival.

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“…In the case of angiogenin, the natural inhibitor is the above mentioned cytosolic protein RNH1 (also called RI, RNH and PRI) which binds the ribonuclease and, indeed, all monomeric members of the pancreatic RNase family with an extraordinarily high affinity [222]. RNH1 is found mainly in the cytosol but small amounts are also present in the mitochondria and nucleus [223]. The interaction between RNH1 and angiogenin is one of the strongest protein interactions discovered thus far, with a K i value of 10 −13 − 10 −16 correlating with a complex half-life of several days [220,221,224].…”

Section: Targeted Cell Depletion Using Human Angiogeninmentioning

confidence: 99%

Engineered Versions of Granzyme B and Angiogenin Overcome Intrinsic Resistance to Apoptosis Mediated by Human Cytolytic Fusion Proteins

Cremer

Hehmann-Titt²,

Schiffer

et al. 2015

Resistance to Targeted Anti-Cancer Therapeutics

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The use of therapies based on antibody fusion proteins for the selective elimination of tumor cells has increased markedly over the last two decades because the severe side effects associated with conventional chemotherapy and radiotherapy are reduced or even eliminated. However, the initial development of immunotoxins suffered from a number of drawbacks such as nonspecific cytotoxicity and the induction of immune responses because the components were non-human in origin. The most recent iteration of this approach is a new class of targeted human cytolytic fusion proteins (hCFPs) comprising a tumor-specific targeting component such as a human antibody fragment fused to a human effector domain with pro-apoptotic activity. Certain tumors resist the activity of hCFPs by upregulating the intracellular expression of native inhibitors, which rapidly bind and inactivate the human effector domains. Higher doses of the hCFPs are, therefore, required to improve therapeutic efficacy. To circumvent these inhibitory processes, novel isoforms of the enzymes granzyme B and angiogenin have been designed to increase their intrinsic activity and reduce their interactions with native inhibitors resulting in more potent hCFPs that can be applied at lower doses. This chapter summarizes the basic scientific knowledge that can facilitate the rational development of human enzymes with novel and beneficial characteristics, including the ability to avoid neutralization by native inhibitors

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The ribonuclease/angiogenin inhibitor is also present in mitochondria and nuclei

Cited by 31 publications

References 23 publications

Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation

Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation

Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

Engineered Versions of Granzyme B and Angiogenin Overcome Intrinsic Resistance to Apoptosis Mediated by Human Cytolytic Fusion Proteins

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