Tanaka E M, Gann A A, Gates P B, Brockes J P
Ludwig Institute for Cancer Research, University College London, United Kingdom.
J Cell Biol. 1997 Jan 13;136(1):155-65. doi: 10.1083/jcb.136.1.155.
Withdrawal from the cell cycle is an essential aspect of vertebrate muscle differentiation and requires the retinoblastoma (Rb) protein that inhibits expression of genes needed for cell cycle entry. It was shown recently that cultured myotubes derived from the Rb-/- mouse reenter the cell cycle after serum stimulation (Schneider, J.W., W. Gu, L. Zhu, V. Mahdavi, and B. Nadal-Ginard. 1994. Science (Wash. DC). 264:1467-1471). In contrast with other vertebrates, adult urodele amphibians such as the newt can regenerate their limbs, a process involving cell cycle reentry and local reversal of differentiation. Here we show that myotubes formed in culture from newt limb cells are refractory to several growth factors, but they undergo S phase after serum stimulation and accumulate 4N nuclei. This response to serum is inhibited by contact with mononucleate cells. Despite the phenotypic parallel with Rb-/- mouse myotubes, Rb is expressed in the newt myotubes, and its phosphorylation via cyclin-dependent kinase 4/6 is required for cell cycle reentry. Thus, the postmitotic arrest of urodele myotubes, although intact in certain respects, can be undermined by a pathway that is inactive in other vertebrates. This may be important for the regenerative ability of these animals.
退出细胞周期是脊椎动物肌肉分化的一个重要方面，并且需要视网膜母细胞瘤（Rb）蛋白，该蛋白抑制细胞进入细胞周期所需基因的表达。最近的研究表明，源自Rb基因敲除小鼠的培养肌管在血清刺激后会重新进入细胞周期（施奈德，J.W.，W.顾，L.朱，V.马赫达维，以及B.纳达尔 - 吉纳德。1994年。《科学》（华盛顿特区）。264:1467 - 1471）。与其他脊椎动物不同，成年有尾两栖动物，如蝾螈，可以再生它们的肢体，这一过程涉及细胞周期重新进入和分化的局部逆转。在这里我们表明，从蝾螈肢体细胞在培养中形成的肌管对几种生长因子不敏感，但它们在血清刺激后进入S期并积累4N细胞核。这种对血清的反应被与单核细胞接触所抑制。尽管在表型上与Rb基因敲除小鼠的肌管相似，但Rb在蝾螈肌管中表达，并且其通过细胞周期蛋白依赖性激酶4/6的磷酸化是细胞周期重新进入所必需的。因此，有尾两栖动物肌管的有丝分裂后停滞，尽管在某些方面是完整的，但可以被在其他脊椎动物中不活跃的一条途径所破坏。这可能对这些动物的再生能力很重要。
