Department of Human Genetics, McGill University Health Centre, McGill University, Montreal, Montreal, Quebec, Canada.
Normandie University, INSERM, Unicaen, Caen, France.
Cell Cycle. 2020 Jan;19(2):163-178. doi: 10.1080/15384101.2019.1706903. Epub 2019 Dec 29.
The cell cycle is tightly regulated by cyclins and their catalytic moieties, the cyclin-dependent kinases (CDKs). Cyclin D1, in association with CDK4/6, acts as a mitogenic sensor and integrates extracellular mitogenic signals and cell cycle progression. When deregulated (overexpressed, accumulated, inappropriately located), cyclin D1 becomes an oncogene and is recognized as a driver of solid tumors and hemopathies. Recent studies on the oncogenic roles of cyclin D1 reported non-canonical functions dependent on the partners of cyclin D1 and its location within tumor cells or tissues. Support for these new functions was provided by various mouse models of oncogenesis. Finally, proteomic and transcriptomic data identified complex cyclin D1 networks. This review focuses on these aspects of cyclin D1 pathophysiology, which may be crucial for targeted therapy. aa, amino acid; AR, androgen receptor; ATM, ataxia telangectasia mutant; ATR, ATM and Rad3-related; CDK, cyclin-dependent kinase; ChREBP, carbohydrate response element binding protein; CIP, CDK-interacting protein; CHK1/2, checkpoint kinase 1/2; CKI, CDK inhibitor; DDR, DNA damage response; DMP1, cyclin D-binding myb-like protein; DSB, double-strand DNA break; DNA-PK, DNA-dependent protein kinase; ER, estrogen receptor; FASN, fatty acid synthase; GSK3β, glycogen synthase-3β; HAT, histone acetyltransferase; HDAC, histone deacetylase; HK2, hexokinase 2; HNF4α, and hepatocyte nuclear factor 4α; HR, homologous recombination; IR, ionizing radiation; KIP, kinase inhibitory protein; MCL, mantle cell lymphoma; NHEJ, non-homologous end-joining; PCAF, p300/CREB binding-associated protein; PGC1α, PPARγ co-activator 1α; PEST, proline-glutamic acid-serine-threonine, PK, pyruvate kinase; PPAR, peroxisome proliferator-activated receptor; RB1, retinoblastoma protein; ROS, reactive oxygen species; SRC, steroid receptor coactivator; STAT, signal transducer and activator of transcription; TGFβ, transforming growth factor β; UPS, ubiquitin-proteasome system; USP22, ubiquitin-specific peptidase 22; XPO1 (or CRM1) exportin 1.
细胞周期受细胞周期蛋白及其催化亚基（细胞周期蛋白依赖性激酶，CDK）的严格调控。细胞周期蛋白 D1 与 CDK4/6 结合，作为有丝分裂传感器，整合细胞外有丝分裂信号和细胞周期进程。当细胞周期蛋白 D1 失调（过度表达、积累、定位不当）时，它会成为一种癌基因，并被认为是实体瘤和血液恶性肿瘤的驱动因子。最近关于细胞周期蛋白 D1 的致癌作用的研究报告了依赖于细胞周期蛋白 D1 的伴侣及其在肿瘤细胞或组织内位置的非典型功能。各种致癌的小鼠模型为这些新功能提供了支持。最后，蛋白质组学和转录组学数据确定了复杂的细胞周期蛋白 D1 网络。本综述重点介绍了细胞周期蛋白 D1 病理生理学的这些方面，这对于靶向治疗可能至关重要。aa，氨基酸；AR，雄激素受体；ATM，共济失调毛细血管扩张突变；ATR，ATM 和 Rad3 相关；CDK，细胞周期蛋白依赖性激酶；ChREBP，碳水化合物反应元件结合蛋白；CIP，CDK 相互作用蛋白；CHK1/2，检查点激酶 1/2；CKI，CDK 抑制剂；DDR，DNA 损伤反应；DMP1，细胞周期蛋白 D 结合的 myb 样蛋白；DSB，双链 DNA 断裂；DNA-PK，DNA 依赖性蛋白激酶；ER，雌激素受体；FASN，脂肪酸合酶；GSK3β，糖原合酶-3β；HAT，组蛋白乙酰转移酶；HDAC，组蛋白去乙酰化酶；HK2，己糖激酶 2；HNF4α，肝细胞核因子 4α；HR，同源重组；IR，电离辐射；KIP，激酶抑制蛋白；MCL，套细胞淋巴瘤；NHEJ，非同源末端连接；PCAF，p300/CREB 结合相关蛋白；PGC1α，过氧化物酶体增殖物激活受体γ共激活因子 1α；PEST，脯氨酸-谷氨酸-丝氨酸-苏氨酸，PK，丙酮酸激酶；PPAR，过氧化物酶体增殖物激活受体；RB1，视网膜母细胞瘤蛋白；ROS，活性氧物种；SRC，类固醇受体共激活剂；STAT，信号转导和转录激活因子；TGFβ，转化生长因子 β；UPS，泛素-蛋白酶体系统；USP22，泛素特异性肽酶 22；XPO1（或 CRM1）输出蛋白 1。
