Homeobox containing 1, also known as homeobox telomere-binding protein 1 (HOT1), is a protein that in humans is encoded by the HMBOX1 gene.[1] HMBOX1 directly binds to the double-stranded repeat sequence of telomeres.[2][3]
HMBOX1 has originally been identified to associate with telomeric chromatin in telomerase-positive cancer cells and cancer cells that maintain their telomeres based on the Alternative Lengthening of Telomeres (ALT) mechanism by the 'reverse ChIP' technique PICh (Proteomics of Isolated Chromatin segments).[2] Subsequently, direct binding to telomeric DNA was demonstrated through a co-crystal structure of the DNA-binding domain of HMBOX1 with telomeric DNA.[3] Loss-of-function and gain-of-function experiments classify HMBOX1 as a positive regulator of telomere length.[3][4] HMBOX1 had originally been described as a transcriptional repressor based on reporter gene assays,[5] but genome-wide approaches using RNA-seq and ChIP-seq see little to no such effect at least in several cancer cell lines.[6]
↑Zhou S, Xiao Y, Zhuang Y, Liu Y, Zhao H, Yang H, Xie C, Zhou F, Zhou Y (July 2017). "Knockdown of homeobox containing 1 increases the radiosensitivity of cervical cancer cells through telomere shortening". Oncology Reports. 38 (1): 515–521. doi:10.3892/or.2017.5707. PMID28628186.
↑Chen S, Saiyin H, Zeng X, Xi J, Liu X, Li X, Yu L (2006). "Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity". Cytogenetic and Genome Research. 114 (2): 131–6. doi:10.1159/000093328. PMID16825764.
