The Nuclear Lamina: Protein Accumulation and Disease

Almendáriz-Palacios, Carla; Gillespie, Zoe E.; Janzen, Matthew; Martinez, Valeria; Bridger, Joanna M.; Harkness, Troy A. A.; Mousseau, Darrell D.; Eskiw, Christopher H.

doi:10.3390/biomedicines8070188

Cited by 14 publications

(23 citation statements)

References 193 publications

(220 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nuclear lamina (NL) is an interwoven structure composed of lamins and lamin-associated proteins of the inner nuclear membrane (INM). NL and proteins resident in the INM form a dynamic network that regulates chromatin organization, cell cycle regulation, DNA replication, DNA repair, cell differentiation, and death 68 , 69 . The NL is composed of Lamin A and C, which are the two major splice variants of a single gene ( LMNA ), as well as Lamin B1 and B2 encoded by LMNB1 and LMNB2, respectively 68 , 69 .…”

Section: Discussionmentioning

confidence: 99%

“…NL and proteins resident in the INM form a dynamic network that regulates chromatin organization, cell cycle regulation, DNA replication, DNA repair, cell differentiation, and death 68 , 69 . The NL is composed of Lamin A and C, which are the two major splice variants of a single gene ( LMNA ), as well as Lamin B1 and B2 encoded by LMNB1 and LMNB2, respectively 68 , 69 . Lamins interact with chromatin either directly or indirectly through chromatin-binding proteins.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A prelude to the proximity interaction mapping of CXXC5

Ayaz

Turan

Olgun

et al. 2021

Sci Rep

View full text Add to dashboard Cite

CXXC5 is a member of the zinc-finger CXXC family proteins that interact with unmodified CpG dinucleotides through a conserved ZF-CXXC domain. CXXC5 is involved in the modulation of gene expressions that lead to alterations in diverse cellular events. However, the underlying mechanism of CXXC5-modulated gene expressions remains unclear. Proteins perform their functions in a network of proteins whose identities and amounts change spatiotemporally in response to various stimuli in a lineage-specific manner. Since CXXC5 lacks an intrinsic transcription regulatory function or enzymatic activity but is a DNA binder, CXXC5 by interacting with proteins could act as a scaffold to establish a chromatin state restrictive or permissive for transcription. To initially address this, we utilized the proximity-dependent biotinylation approach. Proximity interaction partners of CXXC5 include DNA and chromatin modifiers, transcription factors/co-regulators, and RNA processors. Of these, CXXC5 through its CXXC domain interacted with EMD, MAZ, and MeCP2. Furthermore, an interplay between CXXC5 and MeCP2 was critical for a subset of CXXC5 target gene expressions. It appears that CXXC5 may act as a nucleation factor in modulating gene expressions. Providing a prelude for CXXC5 actions, our results could also contribute to a better understanding of CXXC5-mediated cellular processes in physiology and pathophysiology.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A prelude to the proximity interaction mapping of CXXC5

Ayaz

Turan

Olgun

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The nuclear lamina was described as a structure underlying the nuclear membrane that coordinates essential processes including DNA repair, genome organization, and epigenetic and transcriptional regulation. Loss of protein regulation (proteostasis) resulted in accumulation of protein aggregates within the lamina, affecting its integrity (29). Given the abundance of HS in the cell nucleus (30) and the high affinity of Hpa2 to HS (13), NM localization may involve the interaction of Hpa2 with HS on the nuclear membrane.…”

Section: Discussionmentioning

confidence: 99%

“…This opens new directions in Hpa2 research and mode of action, which by far is still lacking. Given the significance of the nuclear lamina in pathological conditions such as neurodegenerative diseases and aging (29), NM Hpa2 may turn important in pathologies and genetic disorders other than urofacial syndrome (33), but more work is required to study these aspects in detail.…”

Section: Discussionmentioning

confidence: 99%

A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

et al. 2021

View full text Add to dashboard Cite

Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

show abstract

“…The mammalian target of rapamycin complex I (mTORC1) is associated with cellular health and lifespan, and numerous naturally occurring compounds impact mTORC1 activity [1,27,28]. The mTOR protein is the catalytic kinase subunit of mTORC1 and is activated by phosphorylation (p-mTOR).…”

Section: Phenolic Subclass Impacts Cellular Pathways That Promote Cellular Healthmentioning

confidence: 99%

Haskap Berry Phenolic Subclasses Differentially Impact Cellular Stress Sensing in Primary and Immortalized Dermal Fibroblasts

Zehfus

Gillespie

Almendáriz-Palacios

et al. 2021

Cells

Self Cite

View full text Add to dashboard Cite

It is generally accepted that dietary phenolics from fruits are of significant importance to human health. Unfortunately, there is minimal published data on how differences in phenolic structure(s) impact biological pathways at cellular and molecular levels. We observed that haskap berry extracts isolated with ethanol:formic acid:water or phenolic subclass fractions separated using different concentrations of ethanol (40% and 100%) impacted cell growth in a positive manner. All fractions and extracts significantly increased population doubling times. All extracts and fractions reduced intracellular free radicals; however, there were differences in these effects, indicating different abilities to scavenge free radicals. The extracts and fractions also exhibited differing impacts on transcripts encoding the antioxidant enzymes (CAT, SOD1, GPX1, GSS and HMOX1) and the phosphorylation state of nuclear factor-κB (NF-κB). We further observed that extracts and fractions containing different phenolic structures had divergent impacts on the mammalian target of rapamycin (mTOR) and sirtuin 1 (SIRT1). siRNA-mediated knockdown of SIRT1 transcripts demonstrated that this enzyme is key to eliciting haskap phenolic(s) impact on cells. We postulate that phenolic synergism is of significant importance when evaluating their dietary impact.

show abstract

The Nuclear Lamina: Protein Accumulation and Disease

Cited by 14 publications

References 193 publications

A prelude to the proximity interaction mapping of CXXC5

A prelude to the proximity interaction mapping of CXXC5

A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

Haskap Berry Phenolic Subclasses Differentially Impact Cellular Stress Sensing in Primary and Immortalized Dermal Fibroblasts

Contact Info

Product

Resources

About