Mechanisms of non-metastatic 2 (NME2)-mediated control of metastasis across tumor types

Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Pankaj; Chowdhury, Shantanu

doi:10.1007/s00210-011-0631-0

Cited by 28 publications

(26 citation statements)

References 63 publications

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“…Particularly, functions of NME2 with potential to control aggressive growth of cancer cells needs further study (Thakur et al, 2011). Herein we focus on an emerging aspect where NME2-mediated metastases suppression could involve the human ribonucleoprotein telomerase.…”

Section: Role Of Non-metastatic 2 In Suppression Of Cancer Spread Is mentioning

confidence: 99%

Inhibition of telomerase activity by NME2: impact on metastasis suppression?

Kar

Chowdhury

2014

Naunyn-Schmiedeberg's Arch Pharmacol

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Though anti-metastatic function of non-metastatic 2 (NME2) has been implicated in multiple cancers, mechanisms of metastases control by NME2 are not clearly understood. Recent observations indicating the involvement of telomerase, the ribonucleoprotein required for telomere synthesis, in metastatic outcome are interesting. Notably, though the role of telomerase dysfunction in tumorigenesis is relatively well studied, involvement in metastasis progression is poorly understood. Recent findings demonstrate NME2 presence at telomere ends, association with telomerase, and NME2’s role in inhibition of telomerase activity in cancer cells. These present a novel opportunity to investigate mechanisms underlying NME2-mediated metastasis suppression.

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Section: Role Of Non-metastatic 2 In Suppression Of Cancer Spread Is mentioning

confidence: 99%

Inhibition of telomerase activity by NME2: impact on metastasis suppression?

Kar

Chowdhury

2014

Naunyn-Schmiedeberg's Arch Pharmacol

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“…5 Here, we show the metastatic promoter characteristic of miR-224 promote invasion and migration of tumor cells can be explained by inhibiting non-metastatic cell 2 (NME2) which is a metastatic suppressor gene (MSG). 5 Taken together, the over expression of miR-224 is correlative with stronger metastatic propensity of tumor cells. The possible mechanism of miR-224 mediating metastasis is through inhibiting the metastatic suppressor NME2.…”

Section: Microrna-224 Promotes the Metastasis Of Hepatocellular Carcimentioning

confidence: 96%

“…NME2 is one of the family members of the first discovered metastatic suppressor gene non-metastatic 23 (NM23). 5,6 The expression of NME2 has been shown to be inverse proportional to metastasis. The suppressive expression of NME2 has been found in regionally invasive and metastatic carcinomas.…”

Section: Microrna-224 Promotes the Metastasis Of Hepatocellular Carcimentioning

confidence: 99%

2018 Southern Regional Meeting

2018

Journal of Investigative Medicine

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“…One of the functions of NDPK-A is to inhibit metastasis of tumor cells (37). A fundamental characteristic of highly metastatic tumor cells is their ability to display increased cell growth and migration potential.…”

Section: Ndpk-a Is Degraded Via Ubiquitin Proteasomal Processingmentioning

confidence: 99%

The Ubiquitin E3 Ligase SCF-FBXO24 Recognizes Deacetylated Nucleoside Diphosphate Kinase A To Enhance Its Degradation

Chen

Xiong

et al. 2015

Molecular and Cellular Biology

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The Skp-Cul-F box (SCF) ubiquitin E3 ligase machinery recognizes predominantly phosphodegrons or, less commonly, an (I/L)Q molecular signature within substrates to facilitate their recruitment in mediating protein ubiquitination and degradation. Here, we examined the molecular signals that determine the turnover of the multifunctional enzyme nucleoside diphosphate kinase A (NDPK-A) that controls cell proliferation. NDPK-A protein exhibits a half-life of ϳ6 h in HeLa cells and is targeted for ubiquitylation through actions of the F-box protein FBXO24. SCF-FBXO24 polyubiquitinates NDPK-A at K85, and two NH 2 -terminal residues, L55 and K56, were identified as important molecular sites for FBXO24 interaction. Importantly, K56 acetylation impairs its interaction with FBXO24, and replacing K56 with Q56, an acetylation mimic, reduces NDPK-A FBXO24 binding capacity. The acetyltransferase GCN5 catalyzes K56 acetylation within NDPK-A, thereby stabilizing NDPK-A, whereas GCN5 depletion in cells accelerates NDPK-A degradation. Cellular expression of an NDPK-A acetylation mimic or FBXO24 silencing increases NDPK-A life span which, in turn, impairs cell migration and wound healing. We propose that lysine acetylation when presented in the appropriate context may be recognized by some F-box proteins as a unique inhibitory molecular signal for their recruitment to restrict substrate degradation.T he stability of the majority of cellular regulatory proteins is governed by a ubiquitous disposal apparatus, the ubiquitin proteasome system (1). For proteasomal degradation, the selected protein is processed through a hierarchical, highly controlled and relatively selective system involving a series of enzymatic steps. The substrate is ubiquitinated through sequential activities of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and, finally, a ubiquitin ligase (E3). In the cullin (CUL)-RING ubiquitin ligase superfamily, the E3 complex recognizes a specific substrate by physical interactions using adaptor or receptor-like subunits linked to a scaffold base (2-5). The S-phase kinase-associated protein 1 (Skp1)-cullin 1 (CUL1)-F-box protein (SCF) protein complex is a prototypical multicomponent subfamily of CUL-RING E3 ligases that harbors a key substrate receptor component, the F-box protein, which via Skp1 binds the scaffold protein CUL1. Within the SCF complex, the F-box protein associates with the substrate through its C-terminal substrate binding domain and then binds to Skp1 via its NH 2 -terminal Fbox domain (5). Depending on the nature of the molecular sequence within the substrate-binding pocket, F-box proteins are categorized into FbxL, FbxW, and FbxO subfamilies.An important area of investigation is elucidating the molecular signals that recruit the receptor component of SCF-based E3 ligases, the F-box protein, to their targets. It is generally established that phosphorylation within relatively short motifs (phosphodegrons) are key molecular signatures that facilitate the recruitment of F-box proteins...

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Mechanisms of non-metastatic 2 (NME2)-mediated control of metastasis across tumor types

Cited by 28 publications

References 63 publications

Inhibition of telomerase activity by NME2: impact on metastasis suppression?

Inhibition of telomerase activity by NME2: impact on metastasis suppression?

2018 Southern Regional Meeting

The Ubiquitin E3 Ligase SCF-FBXO24 Recognizes Deacetylated Nucleoside Diphosphate Kinase A To Enhance Its Degradation

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