title: Characterization of interactions between PinX1 and human telomerase subunits hTERT and hTR.
abstract: The addition of telomeric repeats to chromosome ends by the enzyme telomerase is a highly orchestrated process. Although much is known regarding telomerase catalytic activity in vitro, less is known about how this activity is regulated in vivo to ensure proper telomere elongation. One protein that appears to be involved in negatively regulating telomerase function in vivo is PinX1 because overexpression of PinX1 inhibits telomerase activity and causes telomere shortening. To understand the nature of this repression, we characterized the interactions among PinX1 and the core components of telomerase, the human telomerase reverse transcriptase (hTERT) and associated human telomerase RNA (hTR). We now show that in vitro PinX1 binds directly to the hTERT protein subunit, primarily to the hTR-binding domain, as well as to the hTR subunit. However, in a cellular context, the association of PinX1 with hTR is dependent on the presence of hTERT. Taken together, we suggest that PinX1 represses telomerase activity in vivo by binding to the assembled hTERT.hTR complex.
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, 27710, USA.
authors.forename: Soma S R
authors.initials: SS
authors.lastname: Banik
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Counter
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D021122:Protein Subunits; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C440808:PINX1 protein, human; D021122:Protein Subunits; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C039919:RNA, recombinant; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase