Pbxip1, also known as HPIP (hematopoietic pre-B-cell leukemia transcription factor-interacting protein), was initially discovered as a corepressor of pre-B-cell leukemia homeobox 1 (PBX1) with a role in hematopoiesis [2,4]. It is involved in multiple signaling cascades such as TGF-β1, PI3K/AKT, Wnt, mTOR, and Sonic hedgehog signaling pathways, regulating various physiological and cellular processes including normal neuronal development, embryogenesis, endometrium decidualization, and germ cell proliferation [2].

In colorectal cancer, PBXIP1 expression is associated with local and distant metastasis, and high expression is linked to worse overall survival. It might serve as a prognostic and regulatory indicator for epithelial-mesenchymal transition (EMT) processes, with its expression associated with cancer cell subtypes of high baseline Wnt activity [1]. In osteoarthritis, elevated HPIP levels are found in patients, and Col2a1-CreERT2/HPIPf/f mice exhibit skeletal abnormalities. HPIP deficiency in mice protects against developing OA, and in vitro RNA-sequencing and chromatin immunoprecipitation sequencing profiles show that HPIP modulates OA cartilage degeneration through transcriptional activation of Wnt target genes [3].

In summary, Pbxip1 plays essential roles in multiple biological processes and is associated with diseases like colorectal cancer and osteoarthritis. Mouse models, such as gene-knockout (KO) or conditional-knockout (CKO) models in osteoarthritis research, have been crucial in revealing its functions in these disease conditions, helping to understand the underlying mechanisms and potentially providing new therapeutic targets.

References:

1. Ilmer, Matthias, Renz, Bernhard W, Kühn, Florian, Horst, David, Woischke, Christine. 2022. PBXIP1 - An indicator for poor outcome and metastatic spread in colorectal cancer. In Pathology, research and practice, 236, 153993. doi:10.1016/j.prp.2022.153993. https://pubmed.ncbi.nlm.nih.gov/35785747/

2. Khumukcham, Saratchandra Singh, Manavathi, Bramanandam. 2021. Two decades of a protooncogene HPIP/PBXIP1: Uncovering the tale from germ cell to cancer. In Biochimica et biophysica acta. Reviews on cancer, 1876, 188576. doi:10.1016/j.bbcan.2021.188576. https://pubmed.ncbi.nlm.nih.gov/34090932/

3. Ji, Quanbo, Xu, Xiaojie, Kang, Lei, Ye, Qinong, Wang, Yan. 2019. Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis. In Nature communications, 10, 313. doi:10.1038/s41467-018-08277-5. https://pubmed.ncbi.nlm.nih.gov/30659184/

4. Manavathi, Bramanandam, Lo, Dennis, Bugide, Suresh, Weiss, Mitchell J, Humphries, R Keith. 2011. Functional regulation of pre-B-cell leukemia homeobox interacting protein 1 (PBXIP1/HPIP) in erythroid differentiation. In The Journal of biological chemistry, 287, 5600-14. doi:10.1074/jbc.M111.289843. https://pubmed.ncbi.nlm.nih.gov/22187427/