Calcium ions modulate the structure of the intrinsically disordered Nucleobindin-2 protein

Skorupska, Anna; Bystranowska, Dominika; Dąbrowska, Katarzyna; Ożyhar, Andrzej

doi:10.1016/j.ijbiomac.2020.03.110

Cited by 13 publications

(42 citation statements)

References 81 publications

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“…Nucleobindin 2 (NUCB2) was first described in 1994 in KM3 acute lymphoblastic leukemia cell line as a DNA binding/EF-hand/acidic-amino acid-rich protein [ 1 , 2 ]. It has been extensively studied since Oh-I et al identified nesftain-1 as a NUCB2 cleavage product [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

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Dzięgiel

Podhorska‐Okołów

2021

IJMS

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Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.

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Section: Introductionmentioning

confidence: 99%

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

Kmiecik

Dzięgiel

Podhorska‐Okołów

2021

IJMS

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“…Additionally, Nucb2 contains a putative Zn 2+ -binding motif at its N-terminal half, similar to its paralogue Nucb1 [48] . Our previous research showed that Nucb2s from Gallus gallus (ggNucb2) and Homo sapiens (hsNucb2) belong to the family of intrinsically disordered proteins (IDPs) [49] . We also revealed that Ca 2+ binding affects the overall structure of Nucb2 molecules, which leads to their compaction with the simultaneous formation of a mosaic-like structure consisting of intertwined disordered and ordered regions of the initially disordered C-terminal half of apo-Nucb2 [49] .…”

Section: Introductionmentioning

confidence: 99%

Nucleobindin-2 consists of two structural components: The Zn2+-sensitive N-terminal half, consisting of nesfatin-1 and -2, and the Ca2+-sensitive C-terminal half, consisting of nesfatin-3

Bystranowska

Skorupska

Sołtys

et al. 2021

Computational and Structural Biotechnology Journal

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“…Remarkably, the Nucb2–necdin interaction increased the level of Ca 2+ in the cytoplasm [ 8 ]. Nucb2 is a Ca 2+ -binding protein, which probably plays a Ca 2+ -sensor protein role [ 9 ]. Additionally, Nucb2 is localized in the Golgi apparatus [ 51 ], which is a storage compartment of Ca 2+ [ 79 ].…”

Section: Nucb2-protein Interactions In the Regulation Of The Tumorigenesis Processmentioning

confidence: 99%

“…Interestingly, all of these interactions are Ca 2+ -dependent, and associated with the structural rearrangements of the carboxy-terminal part of Nucb2—nesfatin-3. We recently showed that nesfatin-3 possesses IDP properties [ 9 ]. The significant flexibility of IDPs facilitates a variety of interactions with molecular partners [ 98 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Nucb2 was also found to be involved in multiple interactions, e.g., with the tumor necrosis factor receptor 1 [ 7 ] and the growth suppressor necdin protein [ 8 ]. Recently, Nucb2s from Homo sapiens and Gallus gallus were characterized as proteins that exhibit the properties of inherently disordered proteins (IDPs) [ 9 ]. The altered expression of IDPs is involved in the pathogenesis of several diseases, such as Alzheimer’s disease [ 10 ] and cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

Skorupska

Lenda

Ożyhar

et al. 2021

IJMS

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Nucb2 is a multifunctional protein associated with a variety of biological processes. Multiple studies have revealed that Nucb2, and its derivative nesfatin-1, are involved in carcinogenesis. Interestingly, the role of Nucb2/nesfatin-1 in tumorigenesis seems to be dual—both pro-metastatic and anti-metastatic. The implication of Nucb2/nesfatin-1 in carcinogenesis seems to be tissue dependent. Herein, we review the role of Nucb2/nesfatin-1 in both carcinogenesis and the apoptosis process, and we also highlight the multifaceted nature of Nucb2/nesfatin-1.

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Calcium ions modulate the structure of the intrinsically disordered Nucleobindin-2 protein

Cited by 13 publications

References 81 publications

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

Nucleobindin-2 consists of two structural components: The Zn2+-sensitive N-terminal half, consisting of nesfatin-1 and -2, and the Ca2+-sensitive C-terminal half, consisting of nesfatin-3

The Multifaceted Nature of Nucleobindin-2 in Carcinogenesis

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