The Id-protein family in developmental and cancer-associated pathways.
The Id-protein family in developmental and cancer-associated pathways.
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ID蛋白质在发育和癌症相关的途径中。
DOI：
10.1186/s12964-016-0161-y
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发表时间：
2017-01-25
期刊：
影响因子：
--
通讯作者：
Cabrele C
中科院分区：
文献类型：
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作者：
Roschger C;Cabrele C
DNA结合和细胞分化抑制蛋白（Id）是螺旋-环-螺旋（HLH）转录因子大家族的成员，但它们缺乏任何DNA结合基序。在发育过程中，Id蛋白通过直接和间接机制调节不同的细胞周期调节因子，在细胞周期进程和细胞分化的调节中发挥关键作用。到目前为止，已经确定了几种Id-蛋白相互作用的伴侣，它们属于结构和功能无关的家族，包括I类和II类bHLH转录因子、视网膜母细胞瘤蛋白和相关口袋蛋白、配对盒转录因子和26 S蛋白酶体的S5 a亚基等。尽管Id蛋白的HLH结构域参与了它们的大多数蛋白质-蛋白质相互作用事件，但需要位于它们的N-末端和C-末端区域的额外基序来识别不同的蛋白质伴侣。Id蛋白与结构上不同的蛋白相互作用的能力可能源于它们的构象灵活性：事实上，这些蛋白含有内在无序的区域，在HLH区域的情况下，这些区域在自缔合或异缔合时发生折叠。除了它们在发育过程中对细胞命运决定和细胞周期进展的关键作用外，其他重要的细胞事件与许多病理学中的Id蛋白表达有关。Id蛋白表达失调与肿瘤生长、血管形成、侵袭性、转移、化学抗性和干性以及各种发育缺陷和疾病有关。本文就这些调控蛋白的结构特性、作用方式、生物学功能和治疗潜力作一综述。
Inhibitors of DNA binding and cell differentiation (Id) proteins are members of the large family of the helix-loop-helix (HLH) transcription factors, but they lack any DNA-binding motif. During development, the Id proteins play a key role in the regulation of cell-cycle progression and cell differentiation by modulating different cell-cycle regulators both by direct and indirect mechanisms. Several Id-protein interacting partners have been identified thus far, which belong to structurally and functionally unrelated families, including, among others, the class I and II bHLH transcription factors, the retinoblastoma protein and related pocket proteins, the paired-box transcription factors, and the S5a subunit of the 26 S proteasome. Although the HLH domain of the Id proteins is involved in most of their protein-protein interaction events, additional motifs located in their N-terminal and C-terminal regions are required for the recognition of diverse protein partners. The ability of the Id proteins to interact with structurally different proteins is likely to arise from their conformational flexibility: indeed, these proteins contain intrinsically disordered regions that, in the case of the HLH region, undergo folding upon self- or heteroassociation. Besides their crucial role for cell-fate determination and cell-cycle progression during development, other important cellular events have been related to the Id-protein expression in a number of pathologies. Dysregulated Id-protein expression has been associated with tumor growth, vascularization, invasiveness, metastasis, chemoresistance and stemness, as well as with various developmental defects and diseases. Herein we provide an overview on the structural properties, mode of action, biological function and therapeutic potential of these regulatory proteins.