Srfbp1, also known as p49/STRAP, is a transcriptional regulator. It contains a SRF binding domain and a BUD22 domain, and is involved in multiple biological processes. It may regulate genes related to cytoskeletal structure, muscle-specific genes, and is associated with pathways like ribosome biogenesis, which affects growth rate and cell size [2,3,6,7].

In the context of HCV infection, Srfbp1 is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes, acting as an HCV-specific, pan-genotypic host entry factor [1,5].

In aging-related studies, overexpression of Srfbp1 in mice caused deacetylation of histone H4 on lysine 16, suppressed the expression of PGC-1α, mitofusin-1 and mitofusin-2, reduced mitochondrial size, membrane potential and oxygen consumption rate. Its expression was increased in old mouse hearts and in cultured human umbilical vein endothelial cells with advancing population doubling levels, suggesting it may impact mitochondrial dynamics and function during mammalian senescence [2].

In addition, Srfbp1 may be involved in the redistribution of cytoskeletal F-actin proteins during glucose deprivation, as its increased expression correlated with f-actin redistribution genes [3]. Whole exome sequencing also identified Srfbp1 as a novel candidate gene in a POAG family, and its expression was significantly altered in glaucoma [4].

In summary, Srfbp1 plays diverse roles in biological processes such as viral entry, aging-related mitochondrial function, cytoskeletal protein redistribution, and may be associated with glaucoma. Studies on Srfbp1 using in vivo models like mice help to understand its functions in these specific disease-related contexts, providing insights into the underlying molecular mechanisms and potential therapeutic targets.

References:

1. Fénéant, Lucie, Cocquerel, Laurence. 2015. SRFBP1, an Additional Player in HCV Entry. In Trends in microbiology, 23, 590-593. doi:10.1016/j.tim.2015.08.003. https://pubmed.ncbi.nlm.nih.gov/26319372/

2. Zhang, Xiaomin, Williams, Emmanuel D, Azhar, Gohar, Rogers, Steven C, Wei, Jeanne Y. 2016. Does p49/STRAP, a SRF-binding protein (SRFBP1), modulate cardiac mitochondrial function in aging? In Experimental gerontology, 82, 150-9. doi:10.1016/j.exger.2016.06.008. https://pubmed.ncbi.nlm.nih.gov/27337995/

3. Williams, E D, Rogers, S C, Zhang, X, Azhar, G, Wei, J Y. . p49/STRAP, a Serum Response Factor Binding Protein (SRFBP1), Is Involved in the Redistribution of Cytoskeletal F-Actin Proteins during Glucose Deprivation. In The journal of nutrition, health & aging, 21, 1142-1150. doi:10.1007/s12603-017-0925-0. https://pubmed.ncbi.nlm.nih.gov/29188873/

4. Narta, Kiran, Teltumbade, Manoj Ramesh, Vishal, Mansi, Ray, Kunal, Mukhopadhyay, Arijit. 2023. Whole Exome Sequencing Reveals Novel Candidate Genes in Familial Forms of Glaucomatous Neurodegeneration. In Genes, 14, . doi:10.3390/genes14020495. https://pubmed.ncbi.nlm.nih.gov/36833422/

5. Gerold, Gisa, Meissner, Felix, Bruening, Janina, Rice, Charles M, Pietschmann, Thomas. 2015. Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry. In Cell reports, 12, 864-78. doi:10.1016/j.celrep.2015.06.063. https://pubmed.ncbi.nlm.nih.gov/26212323/

6. Zhang, Xiaomin, Azhar, Gohar, Helms, Scott, Zhong, Ying, Wei, Jeanne Y. 2008. Identification of a subunit of NADH-dehydrogenase as a p49/STRAP-binding protein. In BMC cell biology, 9, 8. doi:10.1186/1471-2121-9-8. https://pubmed.ncbi.nlm.nih.gov/18230186/

7. Zhang, Xiaomin, Azhar, Gohar, Rogers, Steven C, Luo, Shaoke, Wei, Jeanne Y. 2014. Overexpression of p49/STRAP alters cellular cytoskeletal structure and gross anatomy in mice. In BMC cell biology, 15, 32. doi:10.1186/1471-2121-15-32. https://pubmed.ncbi.nlm.nih.gov/25183317/