The role of posttranslational modification in moonlighting glyceraldehyde-3-phosphate dehydrogenase structure and function.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a moonlighting protein exhibiting distinct activities apart from its classical role in glycolysis. Regulation of its moonlighting functions and its subcellular localization may be dependent on its posttranslational modification (PTM). The latter include its phosphorylation, which is required for its role in intermembrane trafficking, synaptic transmission and cancer survival; nitrosylation, which is required for its function in apoptosis, heme metabolism and the immune response; acetylation which is necessary for its modulation of apoptotic gene regulation; and N-acetylglucosamine modification which may induce changes in GAPDH oligomeric structure.

Moonlighting glyceraldehyde-3-phosphate dehydrogenase: posttranslational modification, protein and nucleic acid interactions in normal cells and in human pathology.

Moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibits multiple functions separate and distinct from its historic role in energy production. Further, it exhibits dynamic changes in its subcellular localization which is an a priori requirement for its multiple activities. Separately, moonlighting GAPDH may function in the pathology of human disease, involved in tumorigenesis, diabetes, and age-related neurodegenerative disorders.

Pleiotropic effects of moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cancer progression, invasiveness, and metastases.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may represent the quintessential example of a moonlighting protein. The latter are a new, intriguing class of cell proteins which exhibit multiple activities in different subcellular locales apart from their initially, well-characterized function. As such, apart from its classical role in energy production, membrane-bound GAPDH is required for membrane fusion, endocytosis and, intriguingly, for iron transport.

Structural analysis of glyceraldehyde-3-phosphate dehydrogenase functional diversity.

Multifunctional proteins provide a new mechanism to expand exponentially cell information and capability beyond that indicated by conventional gene analyses. As such, examination of their structure-function relationships provides a means to define the mechanisms through which cells accomplish critical yet disparate activities required for cell viability and survival. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may be considered the quintessential multidimensional protein which exhibits a variety of functions unrelated to its classical role in energy production.

Subcellular dynamics of multifunctional protein regulation: mechanisms of GAPDH intracellular translocation.

Multidimensional proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibit distinct activities unrelated to their originally identified functions. Apart from glycolysis, GAPDH participates in iron metabolism, membrane trafficking, histone biosynthesis, the maintenance of DNA integrity and receptor mediated cell signaling. Further, multifunctional proteins exhibit distinct changes in their subcellular localization reflecting their new activities.

On the functional diversity of glyceraldehyde-3-phosphate dehydrogenase: biochemical mechanisms and regulatory control.

Background: New studies provide evidence that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is not simply a classical glycolytic protein of little interest. Instead, it is a multifunctional protein with significant activity in a number of fundamental cell pathways. GAPDH is a highly conserved gene and protein, with a single mRNA transcribed from a unique gene.

New nuclear functions of the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase, in mammalian cells.

Recent studies establish that the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is not simply a classical metabolic protein involved in energy production. Instead, it is a multifunctional protein with defined functions in numerous subcellular processes. New investigations establish a primary role for GAPDH in a variety of critical nuclear pathways apart from its already recognized role in apoptosis.

Aging of human glyceraldehyde-3-phosphate dehydrogenase is dependent on its subcellular localization.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), long considered a traditional glycolytic protein, displays multiple activities independent of its role in energy generation. This functional diversity is dependent on its membrane, cytoplasmic or nuclear localization. GAPDH is encoded by one active gene and is synthesized as a single 37 kDa protein without alternate splicing.

Subcellular analysis of aberrant protein structure in age-related neurodegenerative disorders.

Subcellular interactions of neurodegenerative disease proteins may provide a basic molecular mechanism underlying neuronal disorders. Each protein may also exhibit activities related to normal cell structure and function. It may be necessary to develop methodologies to distinguish between normal and abnormal intracellular interactions of such proteins in human cells.

Subcellular localization of human glyceraldehyde-3-phosphate dehydrogenase is independent of its glycolytic function.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was considered a classical glycolytic protein involved exclusively in cytosolic energy production. However, recent evidence suggests that it is a multifunctional protein displaying diverse activities distinct from its conventional metabolic role. These new roles for GAPDH may be dependent on its subcellular localization, oligomeric state or on the proliferative state of the cell.

Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer's disease fibroblasts.

The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been implicated both in age-related neurodegenerative disease and in apoptosis. Previous in vitro studies suggest an interaction between GAPDH and the beta-amyloid precursor protein (beta-APP), a protein directly involved in Alzheimer's disease (AD). New studies indicate that GAPDH is a multidimensional protein with diverse membrane, cytoplasmic, and nuclear functions; each is distinct from its role in glycolysis.

Alteration of intracellular structure and function of glyceraldehyde-3-phosphate dehydrogenase: a common phenotype of neurodegenerative disorders?

Recent evidence reveals that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is not simply a classical glycolytic protein of little interest. Instead, it is a multifunctional protein with diverse cytoplasmic, membrane and nuclear activities. Significantly, each activity is separate and distinctfrom its role in energy production.

Alteration of nuclear glyceraldehyde-3-phosphate dehydrogenase structure in Huntington's disease fibroblasts.

The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may be involved in neuronal disease and in programmed cell death. Recent investigations indicate an in vitro physical association between GAPDH and huntingtin, the mutated protein in Huntington's disease (HD). Previous studies reveal the functional diversity of GAPDH as a membrane, cytoplasmic and nuclear protein.