Department of Hematology, University Hospital of Ioannina, Greece.
Br J Cancer. 2012 Oct 9;107(8):1423-32. doi: 10.1038/bjc.2012.380. Epub 2012 Sep 6.
Prolyl hydroxylation is a post-translational modification that affects the structure, stability and function of proteins including collagen by catalysing hydroxylation of proline to hydroxyproline through action of collagen prolyl hydroxylases3 (C-P3H) and 4 (C-P4H). Three C-P3Hs (nomenclature was amended according to approval by the HGNC symbols and names at http://www.genenames.org/ and Entrez database at http://www.ncbi.nlm.nih.gov/gene) leucineproline-enriched proteoglycan (leprecan) 1 (Lepre1), leprecan-like 1 (Leprel1), leprecan-like 2 (Leprel2) and two paralogs Cartilage-Related Protein (CRTAP) and leprecan-like 4 (Leprel4) are found in humans. The C-P4Hs are tetrameric proteins comprising a variable α subunit, encoded by the P4HA1, P4HA2 and P4HA3 genes and a constant β subunit encoded by P4HB.
We used RT-PCR, qPCR, pyrosequencing, methylation-specific PCR, western blotting and immunohistochemistry to investigate expression and regulation of the C-P3H and C-P4H genes in B lymphomas and normal bone marrow.
C-P3H and C-P4H are downregulated in lymphoma. Down-regulation is associated with methylation in the CpG islands and is detected in almost all common types of B-cell lymphoma, but the CpG islands are unmethylated or methylated at lower levels in DNA isolated from normal bone marrow and lymphoblastoid cell lines. Methylation of multiple C-P3H and C-P4H genes is present in some lymphomas, particularly Burkitt's lymphoma.
Methylation of C-P3H and C-P4H is common in B lymphomas and may have utility in differentiating disease subtypes.
脯氨酰羟化作用是一种翻译后修饰，通过胶原蛋白脯氨酰羟化酶 3（C-P3H）和 4（C-P4H）的作用，将脯氨酸羟化为羟脯氨酸，从而影响包括胶原蛋白在内的蛋白质的结构、稳定性和功能。三种 C-P3H（命名法根据 HGNC 符号和名称的批准进行了修订，网址为 http://www.genenames.org/，Entrez 数据库网址为 http://www.ncbi.nlm.nih.gov/gene）：富含亮氨酸脯氨酸的蛋白聚糖（leprecan）1（Lepre1）、leprecan-like 1（Leprel1）、leprecan-like 2（Leprel2）和两个 paralogs Cartilage-Related Protein（CRTAP）和 leprecan-like 4（Leprel4）在人类中发现。C-P4H 是由可变的α亚基和一个恒定的β亚基组成的四聚体蛋白，α亚基由 P4HA1、P4HA2 和 P4HA3 基因编码，β亚基由 P4HB 基因编码。
我们使用 RT-PCR、qPCR、焦磷酸测序、甲基化特异性 PCR、western blot 和免疫组织化学方法研究了 C-P3H 和 C-P4H 基因在 B 淋巴瘤和正常骨髓中的表达和调控。
C-P3H 和 C-P4H 在淋巴瘤中下调。下调与 CpG 岛的甲基化有关，几乎在所有常见的 B 细胞淋巴瘤中都能检测到，但 CpG 岛在正常骨髓和淋巴母细胞系分离的 DNA 中未甲基化或低甲基化。一些淋巴瘤中存在多个 C-P3H 和 C-P4H 基因的甲基化，特别是伯基特淋巴瘤。
C-P3H 和 C-P4H 的甲基化在 B 淋巴瘤中很常见，可能对区分疾病亚型有一定的作用。
