HMBOX1

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
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHMBOX1, HNF1LA, HOT1, PBHNF, homeobox containing 1, TAH1
External IDsMGI: 2445066 HomoloGene: 11589 GeneCards: HMBOX1
Orthologs
SpeciesHumanMouse
Entrez

79618

219150

Ensembl

ENSG00000147421

ENSMUSG00000021972

UniProt

Q6NT76

Q8BJA3

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

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

  1. GRCh38: Ensembl release 89: ENSG00000147421 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000021972 - Ensembl, 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. 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. 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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