Note | NS5ATP9, Hepatitis C virus NS5A-transactivated protein 9, HCV NS5A-transactivated protein 9, Overexpressed in anaplastic thyroid carcinoma-1, OEATC-1, OEATC1, p15(PAF), L5. |
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| Protein diagram. 111 aa in length, single transcript, mutation I-A at position 65 and mutation F-A at position 68 results in loss of PCNA binding. |
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Description | The KIAA0101 gene encodes for a 111 amino acid 15 kDa protein. It contains a conserved proliferating cell nuclear antigen (PCNA)-binding motif (Yu et al., 2001). |
Expression | Predominant expression in liver, pancreas and brain. Not detected in heart or liver (Yu et al., 2001). The KIAA0101 protein was down-regulated in human hepatocellular carcinoma (Guo et al., 2006; Yuan et al., 2007). Increased protein levels have been detected in pancreatic cancer cells (Hosokawa et al., 2007). |
Localisation | Nucleus, mitochondrion (Yu et al., 2001; Guo et al., 2006; Simpson et al., 2006; Yuan et al., 2007). |
Function | The KIAA0101 protein binds to PCNA through a conserved PCNA binding domain. PCNA is required for DNA replication or repair as a supplementary factor for DNA polymerase (Paunesku et al., 2001). Proteins bound to PCNA can prevent its binding to DNA polymerase, in turn leading to inhibition of DNA synthesis, cell cycle progression and G1 cell cycle arrest (Yuan et al., 2007). PCNA binding proteins also interact with each other to modulate this regulation. For example, KIAA0101 also interacts in a complex with p33ING1 isoform 2, another PCNA binding protein which is a potential tumor suppressor and regulator of p53 (Simpson et al., 2006). UV irradiation caused increased association of KIAA0101 with PCNA suggesting that this association occurs in response to DNA damage. KIAA0101 also competes with p21WAF for binding to PCNA (Yu et al., 2001). KIAA0101 most recently been shown to act in concert with ATF3 to control genomic integrity after UV stress (Turchi et al., 2009). KIAA0101 expression levels are also regulated by NF-kappaB, this protein family having significant roles in apoptosis, cell cycle regulation and onocgenesis (Hosokawa et al., 2007; Li et al., 2008). Together this data suggests a likely role for KIAA0101 in DNA repair and in protection from UV-induced cell death. |
High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma. |
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PMID 17717129 |
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KIAA0101 (OEACT-1), an expressionally down-regulated and growth-inhibitory gene in human hepatocellular carcinoma. |
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PMID 16646990 |
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Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer. |
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Cancer Res. 2007 Mar 15;67(6):2568-76. |
PMID 17363575 |
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NS5ATP9 gene regulated by NF-kappaB signal pathway. |
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PMID 18727915 |
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PMID 17960622 |
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PMID 20646288 |
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PMID 15789362 |
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PMID 7788527 |
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PMID 11682006 |
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NS5ATP9, a gene up-regulated by HCV NS5A protein. |
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PMID 18068894 |
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The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b. |
Simpson F, Lammerts van Bueren K, Butterfield N, Bennetts JS, Bowles J, Adolphe C, Simms LA, Young J, Walsh MD, Leggett B, Fowles LF, Wicking C. |
Exp Cell Res. 2006 Jan 1;312(1):73-85. Epub 2005 Nov 8. |
PMID 16288740 |
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ATF3 and p15PAF are novel gatekeepers of genomic integrity upon UV stress. |
Turchi L, Fareh M, Aberdam E, Kitajima S, Simpson F, Wicking C, Aberdam D, Virolle T. |
Cell Death Differ. 2009 May;16(5):728-37. Epub 2009 Feb 13. |
PMID 19219066 |
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p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues. |
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Oncogene. 2001 Jan 25;20(4):484-9. |
PMID 11313979 |
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Overexpression of KIAA0101 predicts high stage, early tumor recurrence, and poor prognosis of hepatocellular carcinoma. |
Yuan RH, Jeng YM, Pan HW, Hu FC, Lai PL, Lee PH, Hsu HC. |
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5368-76. |
PMID 17875765 |
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Murine embryonic expression of the gene for the UV-responsive protein p15(PAF). |
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Gene Expr Patterns. 2007 Jan;7(1-2):47-50. Epub 2006 May 25. |
PMID 16815099 |
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