The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: A clue for a role of NOVH in cell-adhesion signaling
The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: A clue for a role of NOVH in cell-adhesion signaling
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DOI：
10.1073/pnas.96.3.869
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发表时间：
1999-02-02
影响因子：
11.1
通讯作者：
Roizman, B
中科院分区：
文献类型：
--
作者：
Perbal, B;Martinerie, C;Roizman, B
NOVH蛋白属于新兴的CCN [结缔组织生长因子（CTGF），Cyr 61/Cef 10，肾母细胞瘤过表达基因]生长调节因子家族，该家族共享显著保守的多模块组织，但表现出独特的功能特征。该家族的两个成员（CYR 61和CTGF）是细胞增殖的正调节剂，而NOVH和另外两个成员（ELM 1和RCOP-1）表现出生长的负调节剂的特征。这些蛋白质的多模块结构表明它们的生物学作用可能取决于与几种因子以及细胞外基质组成蛋白的相互作用。为了深入了解这些结构域的功能，我们使用了一个双杂交系统来识别与NOVH相互作用的蛋白质，我们在这里报告，C-末端结构域赋予全长NOVH蛋白结合fibulin 1C的能力，fibulin 1C是细胞外基质的一种蛋白质，与其他几种细胞粘附调节因子相互作用。此外，我们表明，由表达全长NOVH蛋白的细胞产生的天然N-截短的NOVH同种型也以高亲和力结合纤蛋白1C，并且我们假设NOVH（以及可能的其他CCN蛋白）的截短同种型的产生可能是其生物活性调节的关键方面。这些结果为研究NOVH-纤蛋白1C相互作用及其在正常和病理条件下细胞粘附信号传导中的潜在意义奠定了基础。
The NOVH protein belongs to the emerging CCN [Connective tissue growth factor (CTGF), Cyr61/Cef10, nephroblastoma overexpressed gene] family of growth regulators sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Two members of the family (CYR61 and CTGF) are positive regulators of cell proliferation, whereas NOVH and two other members (ELM1 and RCOP-1) exhibit features of negative regulators of growth. The multimodular structure of these proteins suggests that their biological role(s) may depend on interactions with several factors as well as proteins constitutive of the extracellular matrix. To gain insight into the functionality of these domains, we have used a two-hybrid system to identify proteins interacting with NOVH, We report here that the C-terminal domain confers on the full-length NOVH protein the capacity to bind fibulin 1C, a protein of the extracellular matrix that interacts with several other regulators of cell adhesion. Furthermore, we show that a natural N-truncated isoform of NOVH produced by cells expressing the full-length NOVH protein also binds fibulin 1C with a high affinity, and we hypothesize that the production of truncated isoforms of NOVH (and probably of other CCN proteins) may be a critical aspect in the modulation of their biological activity. These results set the stage for a study of NOVH-fibulin 1C interactions and their potential significance in cell-adhesion signaling in normal and pathological conditions.