Related Experiment Videos

Nm23-H1/NDP kinase folding intermediates and cancer: a hypothesis

Ioan Lascu1

  • 1Institut de Biochimie et Génétique Cellulaires, UMR 5095 University Victor Segalen Bordeaux2 and CNRS, 1, rue Camille Saint-Saëns, 33077, Bordeaux Cedex, France. ioan.lascu@ibgc.u-bordeaux2.fr

Journal of Bioenergetics and Biomembranes
|September 1, 2006
PubMed

Insights

The Nm23-H1/nucleoside diphosphate (NDP) kinase A, a metastasis suppressor, exhibits altered folding in its S120G mutant found in neuroblastomas. This suggests its stability and folding intermediates are crucial for cancer-related regulatory functions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Nm23-H1/nucleoside diphosphate (NDP) kinase A functions as a metastasis suppressor.
  • The S120G mutant form of Nm23-H1/NDP kinase A is associated with high-grade neuroblastomas.
  • Understanding protein folding and stability is critical in cancer biology.

Purpose of the Study:

  • To investigate the folding and refolding pathways of wild-type and S120G mutant Nm23-H1/NDP kinase A.
  • To compare the folding behavior of Nm23-H1/NDP kinase A with typical hexameric NDP kinases.
  • To explore the potential link between protein stability, folding intermediates, and regulatory functions in cancer.

Main Methods:

  • Urea-induced denaturation and in vitro refolding experiments.
  • Size-exclusion chromatography to analyze folding/association pathways.
  • Literature review of protein stability in cancer-related proteins and mutants.

Main Results:

  • Wild-type and S120G mutant Nm23-H1/NDP kinase A unfold and refold via a molten globule intermediate.
  • Unlike typical hexameric NDP kinases, Nm23-H1/NDP kinase A does not unfold into dissociated species and refolds through a native monomeric intermediate.
  • The S120G mutant protein is unable to refold after denaturation.

Conclusions:

  • The folding pathway of Nm23-H1/NDP kinase A, including its molten globule state, differs from typical hexameric NDP kinases.
  • Marginal stability and specific folding intermediates, as observed in Nm23-H1/NDP kinase A and its mutants, may be essential for its metastasis suppressor and regulatory roles in cancer.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...