Absence of PTHrP nuclear localization and C-terminus sequences leads to abnormal development of T cells

Publication date: Available online 10 April 2017
Source:Biochimie
Author(s): Kun-Zhi Jia, Shu-Lei Jin, Chun Yao, Rong Rong, Chong Wang, Pan Du, Wen-Hui Jiang, Xiao-Feng Huang, Qin-Gang Hu, Deng-Shun Miao, Zi-Chun Hua
Parathyroid hormone-related protein (PTHrP), a ubiquitously expressed protein, is composed of four functional domains including N-terminus, mid region, nuclear localization signal (NLS) and C-terminus. Under the direction of NLS, PTHrP can enter cell nucleus from cytoplasm and stimulate mitogenesis. Although PTHrP is considered to have important developmental roles, the role of PTHrP NLS and C-terminus in developmental process remains unknown, especially in T-cell development. Here, we used a knock-in mouse model, which expresses a truncated form of PTHrP missing the NLS (87–107aa) and C-terminus (107–139aa) of the protein, to examine the role of PTHrP NLS and C-terminus in T-cell development. Our results showed that the truncated PTHrP losing the part of 87–139aa led to abnormal subpopulations, impaired proliferation and increased apoptosis in the thymus, indicating that PTHrP is involved in the development of T cells, and the NLS and C-terminus part is necessary for the normal role of PTHrP in T-cell development.



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