Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen Journal Article
| Authors: | Unk, I.; Hajdú, I.; Fátyol, K.; Szakal, B.; Blastyák, A.; Bermudez, V.; Hurwitz, J.; Prakash, L.; Prakash, S.; Haracska, L. |
| Article Title: | Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen |
| Abstract: | Human SHPRH gene is located at the 6q24 chromosomal region, and loss of heterozygosity in this region is seen in a wide variety of cancers. SHPRH is a member of the SWI/SNF family of ATPases/ helicases, and it possesses a C 3HC4 RING motif characteristic of ubiquitin ligase proteins. In both of these features, SHPRH resembles the yeast Rad5 protein, which, together with Mms2-Ubc13, promotes replication through DNA lesions via an error-free post-replicational repair pathway. Genetic evidence in yeast has indicated a role for Rad5 as a ubiquitin ligase in mediating the Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Here we show that SHPRH is a functional homolog of Rad5. Similar to Rad5, SHPRH physically interacts with the Rad6-Rad18 and Mms2-Ubc13 complexes, and we show that SHPRH protein is a ubiquitin ligase indispensable for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Based on these observations, we predict a role for SHPRH in promoting error-free replication through DNA lesions. Such a role for SHPRH is consistent with the observation that this gene is mutated in a number of cancer cell lines, including those from melanomas and ovarian cancers, which raises the strong possibility that SHPRH function is an important deterrent to mutagenesis and carcinogenesis in humans. © 2006 by The National Academy of Sciences of the USA. |
| Keywords: | gene mutation; human cell; nonhuman; ubiquitin; dna replication; dna damage; gene; melanoma; ovary cancer; ubiquitin protein ligase; protein protein interaction; cell line; protein binding; gene function; cancer cell culture; carcinogenesis; dna; ubiquitination; amino acid sequence; molecular sequence data; sequence homology, amino acid; saccharomyces cerevisiae; sequence alignment; tumor suppressor; heterozygosity loss; saccharomyces cerevisiae proteins; cycline; ubiquitin-conjugating enzymes; ubiquitin-protein ligases; adenosine triphosphatases; mutagenesis; dna helicases; chromosome 6q; gene location; ubiquitin conjugating enzyme; proliferating cell nuclear antigen; protein mms2; protein rad1; translesion synthesis; postreplication repair; protein rad5; protein shprh; protein ubc13; shprh gene |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 103 |
| Issue: | 48 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2006-11-28 |
| Start Page: | 18107 |
| End Page: | 18112 |
| Language: | English |
| DOI: | 10.1073/pnas.0608595103 |
| PUBMED: | 17108083 |
| PROVIDER: | scopus |
| PMCID: | PMC1838714 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 64" - "Export Date: 4 June 2012" - "CODEN: PNASA" - "Source: Scopus" |
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