Protein-protein interactions (PPIs) are relationships (i.e. interactions) proteins have with each other. Proteins can interact with each other in a variety of ways, like activating or inactivating each other. Understanding PPIs gives researchers insight into the complex network proteins comprise of. Ultimately, the interaction of proteins defines the fundamental basis of all biological processes. PPIs underlie the functions, processes, and phenotype of organisms, such as with heart formation in humans [1].
Protein-protein interactions of NKX2-5
NKX2-5 is a homeobox transcription factor that is a master regulator of heart formation in humans [2]. Because of its role in regulating the transcription of several genes through DNA-binding, NKX2-5 interacts with myriad proteins. Below, a STRING map of NKX2-5's protein interaction network reveals several proteins which are all linked to proper heart formation in humans. Mutations in the GATA4 and TBX5 genes have recently been shown to interact with NKX2-5 to give rise to deleterious development of the heart in human, possibly giving rise to several defects characteristic of congenital heart disease.
Fig.1
Protein-protein interactions of NKX2-5 with other cells in humans.
http://string-db.org/cgi/network.pl?taskId=BSL92y48QBOK
Discussion
As we can see from the STRING-generated PPI network, NKX2-5 interacts with several proteins. Interestingly, GATA4 and TBX5, along with NKX2-5, were few of the first genes to be linked to congenital heart diseases. Understanding how NKX2-5 interacts with these proteins, in addition to others noted in Fig.1, will enable researchers to better understand how these proteins give rise to CHD. Recent research has suggested that NKX2-5 is an upstream factor of GATA4 and TBX5, and when mutated, gives rises to ectopic levels of TBX5 and GATA4 which ultimately lead to defects in heart formation characteristic of CHD [3].
References
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Elliott DA, Kirk EP, Yeoh T, Chandar S, McKenzie F, Taylor P, Grossfeld P, Fatkin D, Jones O, Hayes P, Feneley M. Cardiac homeobox gene NKX2-5mutations and congenital heart disease. Journal of the American College of Cardiology. 2003 Jun 4;41(11):2072-6.
Linhares VL, Almeida NA, Menezes DC, Elliott DA, Lai D, Beyer EC, de Carvalho AC, Costa MW. Transcriptional regulation of the murine Connexin40 promoter by cardiac factors Nkx2-5, GATA4 and Tbx5. Cardiovascular research. 2004 Dec 1;64(3):402-11.
Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature. 2003 Jul 24;424(6947):443-7.