Sequence and developmental expression ofAmphiTob, an amphioxus homolog of vertebrateTob in thePC3/BTG1/Tob family of tumor suppressor genes

Abstract

Tob is a member of the PC3/BTG1/Tob family of vertebrate tumor suppressor genes; its expression is known to inhibit proliferation of cells in vitro, but its possible roles during normal development have not been investigated previously. The present study concerns the structure and developmental expression of AmphiTob in an invertebrate chordate, amphioxus. This is the first investigation of any Tob gene during embryological development. The 311 amino acid AmphiTob protein is similar to vertebrate Tob but lacks the C‐terminal PQ‐rich domain of the latter. In early embryos of amphioxus, in situ hybridization first reveals AmphiTob expression in the hypoblast at the gastrula stage on the likely dorsal side of the embryo. During subsequent development, expression is seen in several tissues of the ectoderm, mesoderm, and endoderm. The most striking expression domains are in the developing somitic musculature and dorsal nerve cord. In the medial wall of each somite, AmphiTob is expressed strongly by cells destined to differentiate into the axial trunk muscles; this pattern persists until late in the larval stage, evidently because undifferentiated cells are continually becoming myogenic as the muscles grow. Nerve cord cells conspicuously transcribe AmphiTob from the late neurula until the early larval stage: Expression occurs in a few cells scattered along the nerve cord and in a group of cells located in the cerebral vesicle (in a region presumably homologous to the vertebrate diencephalic forebrain). During development, an intense and transitory transcription of AmphiTob may be an early event in cells exiting the cell cycle in preparation for differentiation. Dev. Dyn. 1997;210:11–18. © 1997 Wiley‐Liss, Inc.

Genes modulated by histone acetylation as new effectors of butyrate activity

“…The other gene analyzed is tob‐1 , a member of the recently identified BTG family whose founder gene, BTG1 (B‐cell translocation gene 1), was firstly cloned near the breakpoint of a chromosomal translocation associated to a chronic lymphocytic leukemia [37]. A wealth of evidence suggests that Btg proteins may be mediators of multiple anti‐proliferative activities [28,37–40]. Particularly, Tob‐1 is involved in the arrest of cell cycle at G1/S boundary [28,39] and its expression varies during vertebrate development [40].…”

“…A wealth of evidence suggests that Btg proteins may be mediators of multiple anti‐proliferative activities [28,37–40]. Particularly, Tob‐1 is involved in the arrest of cell cycle at G1/S boundary [28,39] and its expression varies during vertebrate development [40]. It was initially identified as a protein specifically interacting with ErbB‐2 growth factor receptor, and thus it might negatively regulate the proliferative activity of transmembrane protein kinases [28].…”

In search of a function for the TIS21/PC3/BTG1/TOB family

“…Another study showed a modification of APRO2 expression during myogenesis with an increase of its expression during the phase of differentiation of myoblasts into myotubes [23,34]. Finally, xBTG1 ( Xenopus ) and Amphitob ( Amphioxus ) play a role in the control of the embryonic development of these animals [5,35]. On the other hand, several experiments showed that the forced expression of these genes ( APRO1, APRO2, APRO3, APRO4, APRO5, APRO6 ) was more or less anti‐proliferative [3,4,7–9,18,35,36].…”

“…Although the respective approaches to discover the genes/molecules were different, a biological common feature of these gene products was their ability to inhibit cell proliferation. From that time on, other novel related genes were also isolated over the past years using different cloning strategies [5–10]. Since no homology to known functional motifs is evident in their protein sequences of them, it appears likely that these molecules belong to a novel functional class of cell cycle regulators.…”

Interaction of BTG1 and p53-regulatedBTG2 Gene Products with mCaf1, the Murine Homolog of a Component of the Yeast CCR4 Transcriptional Regulatory Complex

“…The antiproliferative activity of this gene, called PC3 (for pheochromocytoma cell-3), and its involvement in cell-cycle regulation, were demonstrated more recently (10). It was also shown that overexpression of the Tob protein inhibits NIH 3T3 cell growth (11), and that its expression varies during amphioxus development (12). As for BTG3, its expression at the end of the G 1 phase has been detected in T lymphocytes (4).…”