Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination Journal Article
| Authors: | Unk, I.; Hajdú, I.; Fátyol, K.; Hurwitz, J.; Yoon, J. H.; Prakash, L.; Prakash, S.; Haracska, L. |
| Article Title: | Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination |
| Abstract: | Human helicase-like transcription factor (HLTF) is frequently inactivated in colorectal and gastric cancers. Here, we show that HLTF is a functional homologue of yeast Rad5 that promotes error-free replication through DNA lesions. HLTF and Rad5 share the same unique structural features, including a RING domain embedded within a SWI/SNF helicase domain and an HIRAN domain. We find that inactivation of HLTF renders human cells sensitive to UV and other DNA-damaging agents and that HLTF complements the UV sensitivity of a rad5Δ yeast strain. Also, similar to Rad5, HLTF physically interacts with the Rad6-Rad18 and Mms2-Ubc13 ubiquitin-conjugating enzyme complexes and promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen at its Lys-164 residue. A requirement of HLTF for error-free postreplication repair of damaged DNA is in keeping with its cancersuppression role. © 2008 by The National Academy of Sciences of the USA. |
| Keywords: | controlled study; unclassified drug; dna binding protein; human cell; genetics; mutation; dna-binding proteins; nonhuman; dna replication; protein domain; protein function; ultraviolet radiation; metabolism; dna damage; ubiquitin protein ligase; protein protein interaction; cell line; protein binding; transcription factor; drug effect; drug resistance; radiation exposure; transcription factors; tumor suppressor gene; ubiquitination; saccharomyces cerevisiae; tumor suppressor; yeast; saccharomyces cerevisiae proteins; cycline; saccharomyces cerevisiae protein; protein structure; ultraviolet rays; adenosine triphosphatase; ubiquitin-conjugating enzymes; polyubiquitin; ubiquitin-protein ligases; adenosine triphosphatases; lysine; ligase; genetic complementation; ubiquitin conjugating enzyme; ligases; proliferating cell nuclear antigen; genetic complementation test; mesylic acid methyl ester; rad18 protein; methyl methanesulfonate; damage bypass; k63 polyubiquitination; yeast rad5; helicase like transcription factor; protein rad5; ubiquitin conjugating enzyme 13; rad18 protein, human; rad5 protein, s cerevisiae; smarca3 protein, human; ube2n protein, human; ube2v2 protein, human |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 105 |
| Issue: | 10 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2008-03-25 |
| Start Page: | 3768 |
| End Page: | 3773 |
| Language: | English |
| DOI: | 10.1073/pnas.0800563105 |
| PUBMED: | 18316726 |
| PROVIDER: | scopus |
| PMCID: | PMC2268824 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 40" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
