Biology:HMBOX1

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


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]

References

  1. "Entrez Gene: Homeobox containing 1". https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=79618. 
  2. 2.0 2.1 "Purification of proteins associated with specific genomic Loci". Cell 136 (1): 175–86. January 2009. doi:10.1016/j.cell.2008.11.045. PMID 19135898. 
  3. 3.0 3.1 3.2 "HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment". The EMBO Journal 32 (12): 1681–701. June 2013. doi:10.1038/emboj.2013.105. PMID 23685356. 
  4. "Knockdown of homeobox containing 1 increases the radiosensitivity of cervical cancer cells through telomere shortening". Oncology Reports 38 (1): 515–521. July 2017. doi:10.3892/or.2017.5707. PMID 28628186. 
  5. "Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity". Cytogenetic and Genome Research 114 (2): 131–6. 2006. doi:10.1159/000093328. PMID 16825764. 
  6. "ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator". EMBO Reports 18 (6): 929–946. June 2017. doi:10.15252/embr.201744095. PMID 28500257. 

Further reading