JUNB属于AP-1转录因子家族，该家族成员均为碱性亮氨酸拉链（bZIP）蛋白，能够形成同源或异源二聚体并结合DNA调控基因表达。JUNB在细胞增殖、分化、凋亡和免疫应答等多种生物学过程中发挥关键作用。它主要通过与FOS家族蛋白形成异源二聚体（如JUNB-FOS）来识别并结合靶基因启动子区域的AP-1位点（TGACTCA序列），从而调控下游基因的转录。JUNB的表达产物具有抑制细胞周期进程的特性，尤其在G1/S期转换中起负调控作用，这与家族成员c-JUN的促增殖功能形成对比。JUNB突变可能导致其DNA结合能力或二聚化能力受损，进而影响其对靶基因的调控，例如在骨髓增生异常综合征中已发现JUNB功能缺失突变与疾病进展相关。该基因与多种疾病存在关联，包括癌症（如乳腺癌中JUNB低表达与不良预后相关）、自身免疫性疾病（通过调控IL-4等细胞因子）和心血管疾病（参与血管平滑肌细胞表型转换）。当JUNB过表达时，会抑制细胞增殖并促进分化，如在角质形成细胞中可加速终末分化；而在造血系统中过表达可能导致髓系分化异常。相反，JUNB表达降低会解除其对细胞周期的抑制，促进肿瘤发生，并影响TH2型免疫反应（因失去对IL-4的调控）。AP-1家族成员（包括JUN、FOS、ATF亚家族）的共性是均含bZIP结构域，通过不同组合形成具有特定靶向性的二聚体，在应激反应、发育和致癌转化等过程中扮演核心角色。值得注意的是，JUNB对AP-1活性具有双向调节作用，既可激活某些靶基因，又能通过竞争性抑制其他AP-1成分（如c-JUN）发挥抑制作用。

JUNB encodes a member of the AP-1 transcription factor family, which comprises basic leucine zipper (bZIP) proteins capable of forming homo- or heterodimers to bind DNA and regulate gene expression. Functionally, JUNB primarily acts as a negative regulator of cell proliferation, particularly at the G1/S transition, contrasting with the pro-proliferative role of its family member c-JUN; it achieves this by forming heterodimers with FOS family proteins to recognize and bind AP-1 sites (TGACTCA) in target gene promoters. This dual regulatory capacity allows JUNB to both activate specific target genes and competitively inhibit other AP-1 components, such as c-JUN, thereby modulating cellular responses to stress, development, and carcinogenic transformation. In terms of tissue-specific effects, overexpression of JUNB suppresses proliferation and promotes differentiation, such as accelerating terminal differentiation in keratinocytes, whereas its downregulation relieves cell cycle inhibition, potentially promoting tumorigenesis and altering TH2-type immune responses by disrupting the regulation of cytokines like IL-4. Conversely, in the hematopoietic system, JUNB overexpression can lead to myeloid differentiation abnormalities. Clinically, JUNB is implicated in various pathologies, including cancer (where low expression in breast cancer correlates with poor prognosis), autoimmune diseases, and cardiovascular disorders involving vascular smooth muscle cell phenotype switching. Mutations in JUNB that impair its DNA-binding or dimerization capabilities have been linked to disease progression, notably in myelodysplastic syndromes, underscoring its critical role in maintaining genomic stability and proper cellular homeostasis.

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