Opposing roles of pRB and p107 in adipocyte differentiation
Opposing roles of pRB and p107 in adipocyte differentiation
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DOI：
10.1073/pnas.190343597
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发表时间：
2000-09-26
影响因子：
11.1
通讯作者：
Harlow, E
中科院分区：
文献类型：
--
作者：
Classon, M;Kennedy, BK;Harlow, E
视网膜母细胞瘤 (RB) 蛋白家族、pRB、p107。和 p130 被认为在调节细胞周期 G(1) 期进程的能力方面是部分冗余的。然而，pRB 作为经典肿瘤抑制因子的能力似乎是独一无二的，可能是因为它在维持增殖和分化之间的平衡方面具有特殊作用。事实上，各种研究已经揭示了 pRB 在细胞分化和发育中的明显作用。然而，p107 和 p130 在分化中的作用尚未确定，敲除小鼠研究表明它们在发育过程中可能在功能上冗余，并且可能在分化中发挥与 pRB 不同的作用。使用脂肪生成作为模型，我们确实发现了 pRB 家族蛋白在调节分化中的独特作用。缺乏p107和p130的3T3成纤维细胞能够高效分化，而pRB(-/-) 3T3细胞则表现出分化潜力缺陷。而且。 pRB 在野生型细胞中的过度表达促进分化，而 p107 的过度表达则拮抗分化。 pRB 家族成员在脂肪细胞分化中看似相反的作用可以至少部分地通过 pRB 在维持细胞周期退出以及增强分化相关转录因子的活性方面的需要来解释。 C/EBP 阿尔法。 p107 不影响 C/EBP α 驱动的转录，并且不是细胞周期退出所必需的，但 p107 的缺失会降低对分化因子 PPAR γ 的需求。这些发现表明 pRB 蛋白家族各个成员的生物学作用不同，这可能解释了为什么在人类肿瘤发展过程中 pRB 而不是 p107 通常会发生突变。
The retinoblastoma (RB) family of proteins, pRB, p107. and p130, have been postulated to be partially redundant in their ability to regulate progression through the G(1) phase of the cell cycle. However, pRB appears to be unique in its capacity as a classical tumor suppressor, possibly because of a specialized role in maintaining the balance between proliferation and differentiation. A variety of studies have in fact revealed an apparent role for pRB in cellular differentiation and development. However, roles for p107 and p130 in differentiation have not yet been established, and knockout mouse studies have indicated that they may be functionally redundant during development, and possibly perform a role in differentiation distinct from that of pRB. Using adipogenesis as a model, we have indeed found distinct roles for the pRB family proteins in regulating differentiation. 3T3 fibroblasts deficient in p107 and p130 differentiate with high efficiency, whereas pRB(-/-) 3T3 cells exhibit defects in their differentiation potential. Moreover. over-expression of pRB in wild-type cells promotes differentiation, whereas over-expression of p107 antagonizes differentiation. The seemingly opposing roles of pRB family members in adipocyte differentiation can be explained, at least in part, by a requirement for pRB in maintaining cell cycle exit as well as potentiating the activity of the differentiation-associated transcription factor. C/EBP alpha. p107 does not affect C/EBP alpha-driven transcription and is not required for cell cycle exit, but instead, loss of p107 lowers the requirement for the differentiation factor PPAR gamma. These findings suggest contrasting biological roles for individual members of the pRB family of proteins that may explain why pRB, but not p107, is commonly mutated during human tumor development.