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HMBOX1

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HMBOX1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHMBOX1, HNF1LA, HOT1, PBHNF, homeobox containing 1, TAH1
External IDsMGI: 2445066; HomoloGene: 11589; GeneCards: HMBOX1; OMA:HMBOX1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_177338
NM_001347626
NM_001347627

RefSeq (protein)

NP_001334555
NP_001334556
NP_796312

Location (UCSC)Chr 8: 28.89 – 29.06 MbChr 14: 65.05 – 65.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Homeobox containing 1, also known as homeobox telomere-binding protein 1 (HOT1), is a protein that in humans is encoded by the HMBOX1 gene.[5] HMBOX1 directly binds to the double-stranded repeat sequence of telomeres.[6][7]

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).[6] Subsequently, direct binding to telomeric DNA was demonstrated through a co-crystal structure of the DNA-binding domain of HMBOX1 with telomeric DNA.[7] Loss-of-function and gain-of-function experiments classify HMBOX1 as a positive regulator of telomere length.[7][8] HMBOX1 had originally been described as a transcriptional repressor based on reporter gene assays,[9] but genome-wide approaches using RNA-seq and ChIP-seq see little to no such effect at least in several cancer cell lines.[10]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000147421Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021972Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Homeobox containing 1".
  6. ^ a b Déjardin J, Kingston RE (January 2009). "Purification of proteins associated with specific genomic Loci". Cell. 136 (1): 175–86. doi:10.1016/j.cell.2008.11.045. PMC 3395431. PMID 19135898.
  7. ^ a b c Kappei D, Butter F, Benda C, Scheibe M, Draškovič I, Stevense M, Novo CL, Basquin C, Araki M, Araki K, Krastev DB, Kittler R, Jessberger R, Londoño-Vallejo JA, Mann M, Buchholz F (June 2013). "HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment". The EMBO Journal. 32 (12): 1681–701. doi:10.1038/emboj.2013.105. PMC 3680732. PMID 23685356.
  8. ^ 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. PMID 28628186.
  9. ^ 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. PMID 16825764. S2CID 21067536.
  10. ^ Jahn A, Rane G, Paszkowski-Rogacz M, Sayols S, Bluhm A, Han CT, Draškovič I, Londoño-Vallejo JA, Kumar AP, Buchholz F, Butter F, Kappei D (June 2017). "ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator". EMBO Reports. 18 (6): 929–946. doi:10.15252/embr.201744095. PMC 5452029. PMID 28500257.

Further reading

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