TPPII, MYBBP1A and CDK2 form a protein–protein interaction network

Nahálková, Jarmila; Tomkinson, Birgitta

doi:10.1016/j.abb.2014.09.017

Cited by 8 publications

(9 citation statements)

References 29 publications

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“…TPPII functions downstream of the UPS and it may fulfill double role in the proteolysis and in other cellular functions mediated through protein-protein interactions. The p53 regulation on the transcription level may also be affected through the interaction of TPPII with MYBBP1A [13], which binds to p53 and enhances its transcription [28]. The present study confirmed interactions of TPPII with p53 both in the cytoplasmic and the nuclear subcellular compartments.…”

Section: Discussionsupporting

confidence: 86%

“…It contributes to cellular stress response by the translocation from the cytoplasm into the nucleus upon ROS production and DNA damage [30]. Nahálková and Tomkinson [13] also observed both the cytoplasmic and nuclear interactions of TPPII with MYBBP1A by growing of HEK293 cells at serum-free conditions, which increased the frequency of the nuclear interactions. The nuclear localization of TPPII was confirmed here by the immunofluorescent staining within two cell types and using two different antibodies.…”

Section: Discussionmentioning

confidence: 93%

“…On the cellular level, the model mice showed functional links between TPPII, p53, and NF-jB [8] presented by increasing of p53 expression and the level of NF-jB in T-cells and by decreasing of NF-jB in fibroblasts. The transcription factor NFjB was found to be co-repressed by MYBBP1A [32], which directly interacted with both TPPII and p53 via protein-protein interactions [13,28]. Interestingly, MYBBP1A inhibited apoptosis through an activation of several antiapoptotic factors e.g.…”

Section: Discussionmentioning

confidence: 97%

“…Interestingly, TPPII substrate cholecystokinin [25] is a neuropeptide, which is involved in the release of dopamine within neurons. Another substrate of TPPII, somatostatin peptide (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) has been found to be differentially regulated in 6-hydroxy dopamine (6-OHDA) rat model of Parkinson disease before and after application of L-DOPA [37]. SIRT7 belongs to sirtuin family, which is currently under detailed investigation due to neuroprotective effects of several members [9].…”

Section: Discussionmentioning

confidence: 99%

“…The effect might be mediated through p53 pathway and its activation protein MYBBP1A, which was shown to interact directly with TPPII [13]. Then, the evidence of new protein-protein interaction with broadly studied p53 protein would definitely contribute to the development of knowledge about cellular function of TPPII.…”

Section: Introductionmentioning

confidence: 97%

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Novel protein–protein interactions of TPPII, p53, and SIRT7

Nahálková

2015

Mol Cell Biochem

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Novel protein-protein interactions of TPPII, SIRT7, and p53 were detected by co-immunoprecipitation using both HeLa cell lysates and the cytoplasmic fraction prepared by fractionation of mouse liver tissue. The interactions were further verified in vivo by in situ proximity ligation assay (PLA) within control HEK293 cells transformed with empty vector, highactTPPII HEK293 cells over-expressing murine TPPII displaying high specific enzymatic activity and in lowactTPPII HEK293 cells over-expressing human TPPII having low specific activity of the enzyme. Besides an abundant cytoplasmic localization of TPPII-p53 interaction signal, the nuclear interactions were also demonstrated. The cytoplasmic interactions were likewise detected between TPPII and SIRT7 in control HEK293 and lowactTPPII HEK293 cells. The interactions of SIRT7 with p53 were confirmed in three HEK293 cell transformants as well. The cytoplasmic occurrence of SIRT7 protein was demonstrated by immunofluorescence, when both nucleolar and cytoplasmic signals were identified within HEK293 cells and primary human fibroblasts. The unique cytoplasmic localization of SIRT7 protein was discussed based on an epitope specificity of N-terminus specific SIRT7 antibodies utilized in the present study compared with C-terminus specific antibodies previously used for nuclear detection of SIRT7 by other authors. The epitope sequence of N-terminal antibodies is occurring in all three splicing variants of SIRT7 compared to the epitope of C-terminal antibody, which is specific exclusively to the splicing variant 1. The cytoplasmic localization of p53 detected by immunofluorescence supported the results from its interactions with TPPII and SIRT7 observed by in situ PLA within model cells. Novel interactions of TPPII, p53, and SIRT7 presented in this study might contribute to the knowledge of the regulatory effects of these proteins on apoptotic pathways and to the understanding mechanisms of aging and lifespan regulation.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Novel protein–protein interactions of TPPII, p53, and SIRT7

Nahálková

2015

Mol Cell Biochem

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The protein-interaction network with functional roles in tumorigenesis, neurodegeneration, and aging

Nahálková

2016

Mol Cell Biochem

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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 Aβ 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 Aβ degradation by stimulating the matrix metalloproteinases production suggest a double functional role for CD147. An association of the partial portion of cellular CD147 to γ-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.

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Tripeptidyl-peptidase II: Update on an oldie that still counts

Tomkinson

2019

Biochimie

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TPPII, MYBBP1A and CDK2 form a protein–protein interaction network

Cited by 8 publications

References 29 publications

Novel protein–protein interactions of TPPII, p53, and SIRT7

Novel protein–protein interactions of TPPII, p53, and SIRT7

The protein-interaction network with functional roles in tumorigenesis, neurodegeneration, and aging

Tripeptidyl-peptidase II: Update on an oldie that still counts

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