PCNA clamp associated factor (PCLAF)

PCNA clamp associated factor (PCLAF), also known as KIAA0101 or PAF15, is a small nuclear protein (~15 kDa) that binds to proliferating cell nuclear antigen (PCNA) and plays a key role in DNA replication, DNA repair, and cell cycle progression[1][3][4]. Its interaction with PCNA is essential for recruiting replication and repair factors to DNA and for regulating the switch between error-free and translesion DNA synthesis during DNA damage[2][3][4]. Overexpression of PCLAF is common in a wide range of cancers and is associated with poor prognosis, tumor progression, and increased cell proliferation[1][2][4]. PCLAF is also implicated in oncogenic signaling pathways, including p53-p21, Rb/E2F, NF-κB, WNT/CTNNB1, MEK/ERK, and PI3K/AKT/mTOR pathways[2]. Knockdown or inhibition of PCLAF in cancer cells inhibits cell proliferation, causes cell cycle arrest, and increases apoptosis, suggesting PCLAF as a potential therapeutic target—especially for cancers with high PCLAF expression[1][2]. There are no approved drugs directly targeting PCLAF, but research is ongoing to develop such therapeutics and to clarify its utility as a cancer biomarker[2][4].

Other names

PCNA-associated factorKIAA0101NS5ATP9PAFL5HCV NS5A-transactivated protein 9OEATC-1PAF15p15PAFp15(PAF)Overexpressed in anaplastic thyroid carcinoma 1

Inhibition of PCLAF expression or PCLAF/PCNA interaction blocks cell proliferation, cell cycle progression, and enhances apoptosis in cancer cells[1][2]. PCLAF competition with p21 for PCNA binding modulates DNA replication fidelity and repair[2].