Nuclear localization signal of ING4 plays a key role in its binding to p53

Zhang, Xin; Wang, Kesheng; Wang, Zhiqin; Xu, Lusheng; Wang, Qing-Wan; Chen, Fei; Wei, Dongzhi; Han, Ze‐Guang

doi:10.1016/j.bbrc.2005.04.023

Cited by 70 publications

(76 citation statements)

References 23 publications

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“…A partially overlapping deletion (129-132, KKKG) abrogates the nuclear localization (Unoki et al, 2006), suggesting that KG residues 130-132, rather than KK 129-130, are required for ING4 proper cellular localization. This is in keeping with a previous report showing that mutations of residues 129-130 do not affect nuclear localization of ING4 (Zhang et al, 2005).…”

Section: Discussionsupporting

confidence: 93%

“…The NLS1 domain is responsible for ING4 nuclear localization and interaction with p53 Zhang et al, 2005). The PHD domain, a zinc finger motif present in many nuclear proteins (Bienz, 2006), is involved in interaction with HPH-2 (Ozer et al, 2005) and H3K4me2/3 (Pena et al, 2006;Shi et al, 2006), thus linking ING4 to regulation of gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…These functions are ascribed to the NLS1 and, in particular to amino acids 142-146 (RARSK) (Zhang et al, 2005). This region is retained by all the variants, including the ING4-D4AA, which carries a deletion of amino acids 127-130 (KGKK) within the NLS1 domain.…”

Section: Discussionmentioning

confidence: 99%

“…As this protein contains only the N-terminal 36 amino acids of ING4-WT, it was not further analysed. ING4 has been shown previously to display nuclear localization driven by its bipartite NLS1, a region also important for interaction with p53 (Zhang et al, 2005). A second nuclear localization signal (NLS2), located at the C terminus, has been recently shown not required for ING4 nuclear localization (Unoki et al, 2006).…”

Section: Ing4 Alternative Splicing G Raho Et Almentioning

confidence: 99%

“…ING4 was also isolated through a screening for genes able to suppress loss of contact inhibition without affecting cellular proliferation (Kim et al, 2004). Similarly to the other ING family members, ING4 was described to associate with p53 and to upregulate p53-inducible genes ; this is mediated by the bipartite NLS1, also essential for nuclear localization (Zhang et al, 2005). A second, nonfunctional, NLS2 is located at the C-terminal (Unoki et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

et al. 2007

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Inhibitor of growth (ING)4, member of a gene family encoding potential tumor suppressors, is implicated as a repressor of angiogenesis and tumor growth and suppresses loss of contact inhibition in vitro. Here, we report that ING4 undergoes alternative splicing. Expression analysis identified novel ING4 spliced variant mRNAs encoding proteins devoid of different portions. The ING4 variants were detected in both normal and tumor tissues. The existence of ING4 variants was confirmed by several approaches, including reverse transcriptase-polymerase chain reaction, real-time PCR and in silico experiments. To investigate the functional consequences of alternative splicing the ING4 variant cDNAs were expressed in mammalian cells. Our studies indicated that (i) the ING4 variants do not differ from wild-type in their nuclear localization, interaction with p53 and association to HBO1 complex; and (ii) the ING4-DEx6A variant, devoid of the C-terminal portion, loses the capability to inhibit NF-jB. On the whole our data suggest that alternative splicing could modulate the activity of ING4 tumor suppressor protein.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ing4 Alternative Splicing G Raho Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

et al. 2007

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Nuclear‐Targeting Peptides for Cancer Therapy

Yi,

Hussain,

Zhang

et al. 2024

ChemBioChem

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Nucleus is the central regulator of cells that controls cell proliferation, metabolism, and cell cycle, and is considered the most important organelle in cells. The precision medicine that can achieve nuclear targeting has achieved good therapeutic effects in anti‐tumor therapy. However, the presence of biological barriers such as cell membranes and nuclear membranes in cells limit the delivery of therapeutic agents to the nucleus. Therefore, developing effective nuclear‐targeting drug delivery strategies is particularly important. Nuclear‐targeting peptides are a class of functional peptides that can penetrate cell membranes and target the nucleus. They mainly recognize and bind to the nuclear transport molecules (such as Importin‐α/β) and transport the therapeutic agents to the nucleus through nuclear pore complexes (NPC). This review summarizes the most recent developments of strategies for anti‐tumor therapy utilizing nuclear‐targeting peptides, which will ultimately contribute to the development of more effective nuclear‐targeting strategies to achieve better anti‐tumor outcomes.

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The ING gene family in the regulation of cell growth and tumorigenesis

Coles

Jones

2008

Journal Cellular Physiology

137

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The five members of the inhibitor of growth (ING) gene family have garnered significant interest due to their putative roles as tumor suppressors. However, the precise role(s) of these ING proteins in regulating cell growth and tumorigenesis remains uncertain. Biochemical and molecular biological analysis has revealed that all ING members encode a PHD finger motif proposed to bind methylated histones and phosphoinosital, and all ING proteins have been found as components of large chromatin remodeling complexes that also include histone acetyl transferase (HAT) and histone deacetylase (HDAC) enzymes, suggesting a role for ING proteins in regulating gene transcription. Additionally, the results of forced overexpression studies performed in tissue culture have indicated that several of the ING proteins can interact with the p53 tumor suppressor protein and/or the nuclear factor-kappa B (NF-kB) protein complex. As these ING-associated proteins play well-established roles in numerous cell processes, including DNA repair, cell growth and survival, inflammation, and tumor suppression, several models have been proposed that ING proteins act as key regulators of cell growth not only through their ability to modify gene transcription but also through their ability to alter p53 and NF-kB activity. However, these models have yet to be substantiated by in vivo experimentation. Cancer is a complex genetic disease initiated by cells that have accumulated multiple mutations that ultimately bestow malignant characteristics. With rare exceptions, cancers arise from single somatic cells and their progeny. As the neoplastic cells divide, they accumulate either genetic or epigenetic changes resulting in altered phenotypes that provide various selective advantages to the cell as previously described by Hanahan and Weinberg (2000) and Ponder (2001). One key class of genes altered in cancer is the tumor suppressors. Tumor suppressor proteins have been found to regulate numerous cellular processes, including cell cycle arrest, cell senescence, DNA repair, signal transduction, and apoptosis. Reflecting this wide variety of regulatory effects, tumor suppressors include proteins that are involved in transducing external growth signals into the cell, proteins that sense or respond to genetic or metabolic insult, kinases that regulate the function of other enzymes in the nucleus or cytoplasm, proteins that can alter the cellular location or cellular levels of other regulatory proteins, and transcription factors that alter the expression of genes involved in cell growth or survival. In addition, tumor suppressors include proteins that regulate chromatin remodeling and/or modify histones to alter gene expression, including certain subunits of the ATP-dependent SWI/SNF complex, members of the CHD family of chromo-domain proteins, and more recently, members of the inhibitor of growth (ING) family of histone binding proteins. The first member of the ING gene family was discovered through a subtractive hybridization assay between normal mammary ep...

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Nuclear localization signal of ING4 plays a key role in its binding to p53

Cited by 70 publications

References 23 publications

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

Nuclear‐Targeting Peptides for Cancer Therapy

The ING gene family in the regulation of cell growth and tumorigenesis

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