Calcium and integrin-binding protein 1 is a protein that in humans is encoded by the CIB1gene and is located in Chromosome 15.[5][6][7] The protein encoded by this gene is a member of the calcium-binding protein family. The specific function of this protein has not yet been determined; however this protein is known to interact with DNA-dependent protein kinase and may play a role in kinase-phosphatase regulation of DNA end-joining. This protein also interacts with integrin alpha(IIb)beta(3), which may implicate this protein as a regulatory molecule for alpha(IIb)beta(3).[7]
Structure and function
CIB1 is a small protein with a molecular weight of approximately 22 kDa. It has a conserved calcium-binding EF hand domain, which consists of two alpha-helices connected by a loop.[8][9] CIB1 also has an integrin-binding domain, located near the N-terminus of the protein. In addition, CIB1 has a coiled-coil domain and a C-terminal domain.[8][10][11] CIB1 is involved in regulating cell adhesion, migration, and differentiation, as well as other cellular processes. It interacts with integrins, which are transmembrane receptors that play a key role in cell signaling and adhesion to the extracellular matrix. CIB1 has also been shown to regulate other signaling pathways that are important for cell survival and proliferation.[8] Upregulation of CIB1 expression has been observed in several types of cancer, and it has been implicated in cancer development and progression.[8] CIB1 is involved in several cellular processes that are important for cancer progression, including cell adhesion, migration, and invasion. It has been shown to interact with integrins, which are transmembrane receptors that play a key role in these processes.[8] The structure and function of CIB1 make it an important protein in regulating various cellular processes, including those involved in cancer progression, and targeting it may offer potential therapeutic benefits.
Cancer
CIB1 expression has been observed in several types of cancer, including breast, lung, prostate, ovarian, and pancreatic cancer. In breast cancer, CIB1 expression has been shown to be higher in invasive ductal carcinoma compared to normal breast tissue.[12] High levels of CIB1 expression have also been associated with poor prognosis in breast cancer patients.[12] CIB1 has been implicated in cancer development and progression. In breast cancer, CIB1 has been shown to promote cell proliferation, migration, invasion, and metastasis.[13] CIB1 has also been shown to promote the growth of prostate cancer cells and the invasion of ovarian cancer cells.[13] Targeting CIB1 has been explored as a potential therapeutic strategy for cancer. Small molecule inhibitors of CIB1 have shown promise in preclinical models of breast cancer. Silencing CIB1 expression has also been shown to sensitize cancer cells to chemotherapy and radiation therapy.[14][13]
Male infertility
CIB1 has been implicated in male fertility, specifically in sperm function and motility.[15] CIB1 expression has been detected in human sperm, and its levels have been correlated with sperm motility. CIB1 has also been shown to be present in the acrosome region of the sperm, which plays a critical role in fertilization. Studies in mice have shown that CIB1 deficiency leads to impaired sperm motility and reduced fertility.[8][15] Male mice lacking CIB1 exhibited decreased sperm count and decreased sperm motility, resulting in reduced fertility. CIB1 was also found to be required for the proper formation of the sperm tail, which is critical for sperm motility.[8] In addition, CIB1 has been shown to regulate calcium signaling in sperm, which is important for sperm motility and fertilization. CIB1 interacts with the sperm-specific calcium channel CatSper, which is important for regulating intracellular calcium levels in sperm.[8]
Spermatogenesis
Spermatogenesis is the process of producing mature spermatozoa from spermatogonia, the precursor cells in the testes. This process involves several stages, including mitotic division, meiotic division, and differentiation, which results in the production of four haploid sperm cells from one diploid spermatogonium. CIB1 has been shown to play a critical role in spermatogenesis by regulating the differentiation of spermatogonia into spermatocytes. Studies have shown that CIB1 is expressed in spermatogonia, spermatocytes, and spermatids, indicating its role throughout the entire process of spermatogenesis.[8][15] In mice, CIB1 deficiency has been shown to lead to decreased spermatogonia proliferation and impaired differentiation into spermatocytes, resulting in reduced sperm production and male infertility.[15] In addition, CIB1 has been shown to regulate the expression of genes involved in spermatogenesis, including genes involved in cell proliferation and differentiation.[8][15]
^Hattori A, Seki N, Hayashi A, Kozuma S, Saito T (Aug 2000). "Genomic structure of mouse and human genes for DNA-PKcs interacting protein (KIP)". DNA Seq. 10 (6): 415–8. doi:10.3109/10425170009015612. PMID10826701. S2CID21570442.
Holtrich U, Wolf G, Yuan J, et al. (2000). "Adhesion induced expression of the serine/threonine kinase Fnk in human macrophages". Oncogene. 19 (42): 4832–9. doi:10.1038/sj.onc.1203845. PMID11039900. S2CID25807289.
Hollenbach AD, McPherson CJ, Lagutina I, Grosveld G (2002). "The EF-hand calcium-binding protein calmyrin inhibits the transcriptional and DNA-binding activity of Pax3". Biochim. Biophys. Acta. 1574 (3): 321–8. doi:10.1016/s0167-4781(02)00230-0. PMID11997098.
Ma S, Liu MA, Yuan YL, Erikson RL (2003). "The serum-inducible protein kinase Snk is a G1 phase polo-like kinase that is inhibited by the calcium- and integrin-binding protein CIB". Mol. Cancer Res. 1 (5): 376–84. PMID12651910.
