Condensin complex subunit 2 also known as chromosome-associated protein H (CAP-H) or non-SMC condensin I complex subunit H (NCAPH) is a protein that in humans is encoded by the NCAPH gene. NCAPH is a subunit of condensin I, a large protein complex involved in chromosome condensation. Abnormal expression of NCAPH may be linked to various types of carcinogenesis as a prognostic indicator.[1]
Function[edit]
editNCAPH is a member of the barr protein family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. CAP-H is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization.
Structure and Interactions
edit
As one of the main subunits in the highly conserved SMC condensin I complex in eukaryotes, NCAPH associates with NCAPG, NCAPD2, and the N and C termini of the SMC-4 and SMC-2 proteins. NCAPH creates a bridge between the head groups of the SMC proteins and functions as a kleisin protein.
The interaction between NCAPH and the globular ATPase head binding sites of the C terminus and N terminus of the SMC heterodimer allows condensin to have dynamic properties. The C terminus end of NCAPH assumes a winged-helix conformation, which then associates with either head group of the SMC protein. At the opposite end of the kleisin protein, the N terminus associates with proximal coiled coil of the other SMC protein, and creates a helical bundle.[2] This attribute enables the condensin complex to have open and closed conformations in order to associate with chromatin and aid in proper folding of DNA in the condensation process.[3][4]
Studies suggest that the sub-complex formed between NCAPH and NCAPG is critical for interactions with single-stranded DNA and double-stranded DNA to assist mitotic chromosome assembly in eukaryotes.[3]
Model organisms[edit]
editModel organisms have been used in the study of NCAPH function. A conditional knockout mouse line, called Ncaphtm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and an increased susceptibility to bacterial infection was observed in male animals.
Clinical Significance
editNCAPH may be used as a prognostic indicator of carcinogenesis in humans, as the abnormal over-expression of NCAPH is observed in many cancer types.[5]
Studies show that, in prostate cancer,[1] nasopharyngeal carcinoma,[6] hepatocellular carcinoma,[7] and breast cancers,[8] NCAPH is commonly over-expressed, and may be used as a biomarker for various cancer types and a viable prognostic factor for identification and potential drug targeting.[1]
In colon cancer, NCAPH is shown to be higher expressed in cancerous cells compared to non-cancerous epithelial cells. supplementally, when NCAPH is depleted, studies show a decrease in colon cancer cell proliferation. [5][9] Studies show that high expression of NCAPH in colon cancer and non-small cell lung cancer patients had an increased survival rate than those with lower expressions of NCAPH.[9]
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Article Draft
edit- ^ a b c Cui, Feilun; Hu, Jianpeng; Xu, Zhipeng; Tan, Jian; Tang, Huaming (2019-06-01). "Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer". Oncology Letters. 17 (6): 5768–5776. doi:10.3892/ol.2019.10260. ISSN 1792-1074. PMC 6507296. PMID 31186803.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Palecek, Jan J.; Gruber, Stephan (2015-12). "Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes". Structure. 23 (12): 2183–2190. doi:10.1016/j.str.2015.10.004. ISSN 0969-2126.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Hara, Kodai; Kinoshita, Kazuhisa; Migita, Tomoko; Murakami, Kei; Shimizu, Kenichiro; Takeuchi, Kozo; Hirano, Tatsuya; Hashimoto, Hiroshi (2019-05). "Structural basis of HEAT ‐kleisin interactions in the human condensin I subcomplex". EMBO reports. 20 (5). doi:10.15252/embr.201847183. ISSN 1469-221X. PMC 6501013. PMID 30858338.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Palecek, Jan J.; Gruber, Stephan (2015-12). "Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes". Structure. 23 (12): 2183–2190. doi:10.1016/j.str.2015.10.004. ISSN 0969-2126.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Yin, Liang; Jiang, Li-Ping; Shen, Qiu-Shuo; Xiong, Qiu-Xia; Zhuo, Xiao; Zhang, Long-Long; Yu, Hai-Jing; Guo, Xiang; Luo, Ying; Dong, Jian; Kong, Qing-Peng; Yang, Cui-Ping; Chen, Yong-Bin (2017-03). "NCAPH plays important roles in human colon cancer". Cell Death & Disease. 8 (3): e2680–e2680. doi:10.1038/cddis.2017.88. ISSN 2041-4889. PMC 5386579. PMID 28300828.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Xu, Lina; Jiang, Yi; Zheng, Jun; Xie, Guiyuan; Li, Jiao; Shi, Lei; Fan, Songqing (2013-07). "Aberrant expression of β-catenin and E-cadherin is correlated with poor prognosis of nasopharyngeal cancer". Human Pathology. 44 (7): 1357–1364. doi:10.1016/j.humpath.2012.10.025.
{{cite journal}}: Check date values in:|date=(help) - ^ Sun, Chengjun; Huang, Shanzhou; Wang, Hanyu; Xie, Rongxing; Zhang, Lishan; Zhou, Qi; He, Xiaoshun; Ju, Weiqiang (2019-12). "Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma". Molecular Carcinogenesis. 58 (12): 2266–2275. doi:10.1002/mc.23114. ISSN 0899-1987. PMC 6899668. PMID 31523845.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Lu, Haotian; Shi, Chunying; Wang, Shuang; Yang, Chaochao; Wan, Xueqi; Luo, Yunzhe; Tian, Le; Li, Ling (2020-10-01). "Identification of NCAPH as a biomarker for prognosis of breast cancer". Molecular Biology Reports. 47 (10): 7831–7842. doi:10.1007/s11033-020-05859-9. ISSN 1573-4978.
- ^ a b Xiong, Qiuxia; Fan, Songqing; Duan, Lincan; Liu, Baiyang; Jiang, Xiulin; Chen, Xiaobo; Xiong, Chunyan; Tao, Qingyuan; Wang, Juan; Zhang, Hui; Chen, Chuanjiang; Duan, Yong (2020-10-01). "NCAPH is negatively associated with Mcl‑1 in non‑small cell lung cancer". Molecular Medicine Reports. 22 (4): 2916–2924. doi:10.3892/mmr.2020.11359. ISSN 1791-2997. PMC 7453632. PMID 32945371.
{{cite journal}}: CS1 maint: PMC format (link)