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Tissue specificity and the human protein interaction network.

Bossi A, Lehner B - Mol. Syst. Biol. (2009)

Bottom Line: Most tissue-specific proteins do, however, bind to universally expressed proteins, and so can function by recruiting or modifying core cellular processes.Conversely, most 'housekeeping' proteins that are expressed in all cells also make highly tissue-specific protein interactions.These results suggest a model for the evolution of tissue-specific biology, and show that most, and possibly all, 'housekeeping' proteins actually have important tissue-specific molecular interactions.

View Article: PubMed Central - PubMed

Affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation, UPF, Barcelona, Spain.

ABSTRACT
A protein interaction network describes a set of physical associations that can occur between proteins. However, within any particular cell or tissue only a subset of proteins is expressed and so only a subset of interactions can occur. Integrating interaction and expression data, we analyze here this interplay between protein expression and physical interactions in humans. Proteins only expressed in restricted cell types, like recently evolved proteins, make few physical interactions. Most tissue-specific proteins do, however, bind to universally expressed proteins, and so can function by recruiting or modifying core cellular processes. Conversely, most 'housekeeping' proteins that are expressed in all cells also make highly tissue-specific protein interactions. These results suggest a model for the evolution of tissue-specific biology, and show that most, and possibly all, 'housekeeping' proteins actually have important tissue-specific molecular interactions.

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Most tissue-specific proteins interact with core cellular components, and most housekeeping proteins have tissue-specific physical interactions. (A) The proportion of the most tissue-specific proteins (proteins expressed in only 1–10/79 tissues) that interact with universally expressed housekeeping proteins. (B) The percentage of housekeeping proteins that interact with non-housekeeping proteins. These data are for the complete network. The same analysis is shown for the high-confidence multiple-support network in Supplementary Figure 2. Housekeeping proteins are defined by 10 criteria: (1) this study 79/79 tissues, (2) this study 71–79 tissues, (3) this study 79/79 tissues with reduced expression stringency, (4) this study 71–79 tissues with reduced stringency, (5) this study 79/79 tissues with increased stringency, (6) this study 71–79 tissues with increased stringency, (7) Zhu et al microarray data 18/18 tissues, (8) Zhu et al microarray data 16–18 tissues, (9) Zhu et al EST data 18/18 tissues, (10) Zhu et al EST data 16–18 tissues (Zhu et al, 2008). (C) Many proteins make interactions that can only occur in a subset of the tissues in which they are expressed. The number of tissues in which the interactions of a protein can occur is compared with the number of tissues in which a protein is expressed for proteins falling into each of the eight bins of tissue specificity. Data are shown for the complete network. Data for the filtered multiple-support network and reduced and increased stringency expression thresholds are shown in Supplementary Figure 3.
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f2: Most tissue-specific proteins interact with core cellular components, and most housekeeping proteins have tissue-specific physical interactions. (A) The proportion of the most tissue-specific proteins (proteins expressed in only 1–10/79 tissues) that interact with universally expressed housekeeping proteins. (B) The percentage of housekeeping proteins that interact with non-housekeeping proteins. These data are for the complete network. The same analysis is shown for the high-confidence multiple-support network in Supplementary Figure 2. Housekeeping proteins are defined by 10 criteria: (1) this study 79/79 tissues, (2) this study 71–79 tissues, (3) this study 79/79 tissues with reduced expression stringency, (4) this study 71–79 tissues with reduced stringency, (5) this study 79/79 tissues with increased stringency, (6) this study 71–79 tissues with increased stringency, (7) Zhu et al microarray data 18/18 tissues, (8) Zhu et al microarray data 16–18 tissues, (9) Zhu et al EST data 18/18 tissues, (10) Zhu et al EST data 16–18 tissues (Zhu et al, 2008). (C) Many proteins make interactions that can only occur in a subset of the tissues in which they are expressed. The number of tissues in which the interactions of a protein can occur is compared with the number of tissues in which a protein is expressed for proteins falling into each of the eight bins of tissue specificity. Data are shown for the complete network. Data for the filtered multiple-support network and reduced and increased stringency expression thresholds are shown in Supplementary Figure 3.

Mentions: We next analyzed the extent to which tissue-specific proteins interact with the most widely expressed proteins. We find that even when only considering the most tissue-restricted proteins (proteins expressed in ⩽10/79 tissues), most of them are known to interact directly with universally expressed human proteins (Figure 2A). The same result is seen when only considering high-confidence human protein interactions (Supplementary Figure 2A), and when using diverse definitions of universally expressed proteins (Figure 2A). Thus, most tissue-specific proteins can function by directly contacting components of the core cellular machinery.


Tissue specificity and the human protein interaction network.

Bossi A, Lehner B - Mol. Syst. Biol. (2009)

Most tissue-specific proteins interact with core cellular components, and most housekeeping proteins have tissue-specific physical interactions. (A) The proportion of the most tissue-specific proteins (proteins expressed in only 1–10/79 tissues) that interact with universally expressed housekeeping proteins. (B) The percentage of housekeeping proteins that interact with non-housekeeping proteins. These data are for the complete network. The same analysis is shown for the high-confidence multiple-support network in Supplementary Figure 2. Housekeeping proteins are defined by 10 criteria: (1) this study 79/79 tissues, (2) this study 71–79 tissues, (3) this study 79/79 tissues with reduced expression stringency, (4) this study 71–79 tissues with reduced stringency, (5) this study 79/79 tissues with increased stringency, (6) this study 71–79 tissues with increased stringency, (7) Zhu et al microarray data 18/18 tissues, (8) Zhu et al microarray data 16–18 tissues, (9) Zhu et al EST data 18/18 tissues, (10) Zhu et al EST data 16–18 tissues (Zhu et al, 2008). (C) Many proteins make interactions that can only occur in a subset of the tissues in which they are expressed. The number of tissues in which the interactions of a protein can occur is compared with the number of tissues in which a protein is expressed for proteins falling into each of the eight bins of tissue specificity. Data are shown for the complete network. Data for the filtered multiple-support network and reduced and increased stringency expression thresholds are shown in Supplementary Figure 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2683721&req=5

f2: Most tissue-specific proteins interact with core cellular components, and most housekeeping proteins have tissue-specific physical interactions. (A) The proportion of the most tissue-specific proteins (proteins expressed in only 1–10/79 tissues) that interact with universally expressed housekeeping proteins. (B) The percentage of housekeeping proteins that interact with non-housekeeping proteins. These data are for the complete network. The same analysis is shown for the high-confidence multiple-support network in Supplementary Figure 2. Housekeeping proteins are defined by 10 criteria: (1) this study 79/79 tissues, (2) this study 71–79 tissues, (3) this study 79/79 tissues with reduced expression stringency, (4) this study 71–79 tissues with reduced stringency, (5) this study 79/79 tissues with increased stringency, (6) this study 71–79 tissues with increased stringency, (7) Zhu et al microarray data 18/18 tissues, (8) Zhu et al microarray data 16–18 tissues, (9) Zhu et al EST data 18/18 tissues, (10) Zhu et al EST data 16–18 tissues (Zhu et al, 2008). (C) Many proteins make interactions that can only occur in a subset of the tissues in which they are expressed. The number of tissues in which the interactions of a protein can occur is compared with the number of tissues in which a protein is expressed for proteins falling into each of the eight bins of tissue specificity. Data are shown for the complete network. Data for the filtered multiple-support network and reduced and increased stringency expression thresholds are shown in Supplementary Figure 3.
Mentions: We next analyzed the extent to which tissue-specific proteins interact with the most widely expressed proteins. We find that even when only considering the most tissue-restricted proteins (proteins expressed in ⩽10/79 tissues), most of them are known to interact directly with universally expressed human proteins (Figure 2A). The same result is seen when only considering high-confidence human protein interactions (Supplementary Figure 2A), and when using diverse definitions of universally expressed proteins (Figure 2A). Thus, most tissue-specific proteins can function by directly contacting components of the core cellular machinery.

Bottom Line: Most tissue-specific proteins do, however, bind to universally expressed proteins, and so can function by recruiting or modifying core cellular processes.Conversely, most 'housekeeping' proteins that are expressed in all cells also make highly tissue-specific protein interactions.These results suggest a model for the evolution of tissue-specific biology, and show that most, and possibly all, 'housekeeping' proteins actually have important tissue-specific molecular interactions.

View Article: PubMed Central - PubMed

Affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation, UPF, Barcelona, Spain.

ABSTRACT
A protein interaction network describes a set of physical associations that can occur between proteins. However, within any particular cell or tissue only a subset of proteins is expressed and so only a subset of interactions can occur. Integrating interaction and expression data, we analyze here this interplay between protein expression and physical interactions in humans. Proteins only expressed in restricted cell types, like recently evolved proteins, make few physical interactions. Most tissue-specific proteins do, however, bind to universally expressed proteins, and so can function by recruiting or modifying core cellular processes. Conversely, most 'housekeeping' proteins that are expressed in all cells also make highly tissue-specific protein interactions. These results suggest a model for the evolution of tissue-specific biology, and show that most, and possibly all, 'housekeeping' proteins actually have important tissue-specific molecular interactions.

Show MeSH