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The protein-interaction network with functional roles in tumorigenesis, neurodegeneration, and aging
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2016 (English)In: Molecular and Cellular Biochemistry, ISSN 0300-8177, E-ISSN 1573-4919, Vol. 423, no 1-2, 187-196 p.Article, review/survey (Refereed) Published
Abstract [en]

The present review summarizes the knowledge about a protein-interaction network, which includes proteins with significant functions in the mechanisms of aging and age-related diseases. All the detected interacting proteins TPPII, p53, MYBBP1A, CDK2 and SIRT7, SIRT6, and CD147 are suitable for the development of antitumor therapeutics and treatments for diseases of aging. TPPII and SIRT6 directly affect glucose metabolism which drive malignant growth. In addition, SIRT6 activators are attractive candidates for Alzheimer's disease (AD) due to the protection effect of SIRT6 overexpression from DNA damage. TPPII activity exhibits a decreasing effect on mTOR signaling, and its requirement for the degradation of A beta peptides in the human fibroblasts suggests that it has dual functions in tumorigenesis and AD-related pathology. Likewise, the direct promotion of the invasiveness of breast epithelial cells and the contribution to the A beta degradation by stimulating the matrix metalloproteinases production suggest a double functional role for CD147. An association of the partial portion of cellular CD147 to gamma-secretase further supports the functional relation to AD pathology. The animal and cellular models with downregulated or knockout TPPII, p53, SIRT6, SIRT7, and MYBBP1A expression levels illustrate similar functions of the interacting proteins. They demonstrate similar effects on the length of life span, premature aging, and lipid metabolism. The presented protein-interaction network is relevant to the discoveries of the mechanisms of tumorigenesis, aging, and neurodegeneration.

Place, publisher, year, edition, pages
2016. Vol. 423, no 1-2, 187-196 p.
Keyword [en]
National Category
Cell Biology
URN: urn:nbn:se:uu:diva-308883DOI: 10.1007/s11010-016-2836-5ISI: 000387365600018PubMedID: 27699588OAI: oai:DiVA.org:uu-308883DiVA: diva2:1051131
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2016-12-21Bibliographically approved

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Nahálková, Jarmila
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