PCLAF, also known as PAF15 or KIAA0101, is a cell-cycle regulated protein. It is involved in multiple biological processes. It can interact with PCNA, regulating DNA synthesis, DNA methylation maintenance, and DNA-damage bypass. PCLAF is also associated with pathways like AKT/mTOR, TGF-β, and cell cycle-related pathways, playing an important role in various biological functions and disease-related processes. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be used to study its functions in vivo [3].

In mice, genetic deletion of PCLAF in macrophages inhibits bone marrow adipocyte (BMAd) senescence and delays skeletal aging, suggesting PCLAF is an inducer of BMAd senescence. PCLAF binds to the ADGRL2 receptor to inhibit AKT/mTOR signaling, triggering BMAd senescence which then spreads among osteogenic and osteoclastic cells. Additionally, in lung regeneration, genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis. The PCLAF-DREAM complex transactivates CLIC4, triggering TGF-β signaling activation to promote AT1 cell generation from AT2 cells [1,2].

In conclusion, PCLAF plays crucial roles in multiple biological processes. The use of KO/CKO mouse models has revealed its significant functions in skeletal aging and lung fibrosis. These findings contribute to our understanding of the underlying mechanisms of these diseases and may provide potential therapeutic targets for age-related osteoporosis and lung fibrosis [1,2].

References:

1. Xie, Lingqi, Cheng, Yalun, Hu, Biao, Li, Changjun, Peng, Hui. 2024. PCLAF induces bone marrow adipocyte senescence and contributes to skeletal aging. In Bone research, 12, 38. doi:10.1038/s41413-024-00337-5. https://pubmed.ncbi.nlm.nih.gov/38961077/

2. Kim, Bongjun, Huang, Yuanjian, Ko, Kyung-Pil, Kim, Carla, Park, Jae-Il. 2024. PCLAF-DREAM drives alveolar cell plasticity for lung regeneration. In Nature communications, 15, 9169. doi:10.1038/s41467-024-53330-1. https://pubmed.ncbi.nlm.nih.gov/39448571/

3. Tantiwetrueangdet, Anchalee, Panvichian, Ravat, Sornmayura, Pattana, Leelaudomlipi, Surasak, Macoska, Jill A. 2021. PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues. In BMC cancer, 21, 295. doi:10.1186/s12885-021-07994-3. https://pubmed.ncbi.nlm.nih.gov/33743635/