Nuclear functions of NME proteins

Abstract

The NME family of proteins is composed of 10 isoforms, designated NME1-10, which are diverse in their enzymatic activities and patterns of subcellular localization. Each contains a conserved domain associated with a nucleoside diphosphate kinase (NDPK) function, although not all are catalytically active. Several of the NME isoforms (NME1, NME5, NME7, and NME8) also exhibit a 3′–5′ exonuclease activity, suggesting roles in DNA proofreading and repair. NME1 and NME2 have been shown to translocate to the nucleus, although they lack a canonical nuclear localization signal. Binding of NME1 and NME2 to DNA does not appear to be sequence-specific in a strict sense, but instead is directed to single-stranded regions and/or other non-B-form structures. NME1 and NME2 have been identified as potential canonical transcription factors that regulate gene transcription through their DNA-binding activities. Indeed, the NME1 and NME2 isoforms have been shown to regulate gene expression programs in a number of cellular settings, and this regulatory function has been proposed to underlie their well-recognized ability to suppress the metastatic phenotype of cancer cells. Moreover, NME1 and, more recently, NME3, have been implicated in repair of both single- and double-stranded breaks in DNA. This suggests that reduced expression of NME proteins could contribute to the genomic instability that drives cancer progression. Clearly, a better understanding of the nuclear functions of NME1 and possibly other NME isoforms could provide critical insights into mechanisms underlying malignant progression in cancer. Indeed, clinical data indicate that the subcellular localization of NME1 may be an important prognostic marker in some cancers. This review summarizes putative functions of nuclear NME proteins in DNA binding, transcription, and DNA damage repair, and highlights their possible roles in cancer progression.

Non-translational Connections of eEF1B in the Cytoplasm and Nucleus of Cancer Cells

“…Depletion of nucleoside diphosphate kinase A (NME1) lead to a redistribution of eEF1Bα from the cytoplasm to the endoplasmic reticulum fraction in mouse liver (Bruneel et al, 2011). Importantly, nucleoside diphosphate kinase A can be transferred to the nucleus where it promotes the non-homologous end joining of the DNA doublestrand breaks (Xue et al, 2019) and takes part in transcription (Puts et al, 2018).…”

Serum proteomic approach for differentiation of frail and non-frail elderly

“…The homozygous mutation in NME3 gene was found in fatal neurodegenerative disorder [44]. The pro-inflammatory role of NDK3 in signaling downstream of TLR5, had been recognized in cancer immunotherapies [45]. Present study found 1.31 fold increase in protein levels in frail patients in comparison to non-frail patients.…”

The NDPK/NME superfamily: state of the art

“…[48][49][50][51][52][53][54][55] The interactions of NDPK with components of the cytoskeletal machinery are highly relevant, given the well-established role of the cytoskeleton in cell motility, a critical determinant of the metastasis process. NME1 has also been reported to bind proteins belonging to small and heterotrimeric G-proteins ( [56][57][58][59][60][61] ; and Filic 62 upcoming issue; Abu-Taha et al, 63 this issue), transcriptional complexes ( 64-69 ; Sharma et al, 70 Pandey and Robertson, 71 and Puts et al, 72 all in this issue), and components of signaling pathways of MAPK, [73][74][75] TGF-β [76][77][78] and Notch, 79 as well as other factors promoting invasion and metastasis ( 80,81 ; Ferrucci et al 82 upcoming issue). Accordingly, the list of protein/protein interactions involving NME1 is huge and could yield new information about the anti-metastatic activity of NME1, and more generally about the metastatic process.…”