Dr. Massague and his colleagues found that TGF-jS 
can counteract the inhibitory effect of a growth- 
promoting environment on rat skeletal myoblast dif- 
ferentiation. Induction of myogenic differentiation 
by TGF-/3 occurs with acute down-regulation of 
c-myc and Id, two transcription factors that promote 
cell cycle progression and antagonize myogenic dif- 
ferentiation. These findings suggest that TGF-j8 may 
act as a physiological inducer of myogenic differen- 
tiation. Its growth inhibitory effect may trigger ter- 
minal differentiation with permanent withdrawal 
from the cell cycle. Furthermore these results illus- 
trate how the same factor can simultaneously affect 
cell proliferation and differentiation by controlling 
elements that operate in the crossroad of these two 
important processes. 
Dr. Massague is also Member of the Cell Biology 
and Genetics Program at Memorial Sloan- 
Kettering Cancer Center and Professor of Cell Biol- 
ogy at Cornell University Medical College Gradu- 
ate School, New York City. 
Articles 
Andres, J. L., DeFalcis, D., Noda, M., and Massague, 
J. 1992. Binding of two growth factor families to 
separate domains of the proteoglycan betaglycan. 
J Biol Chem 267:5927-5930. 
Andres, J. L., Ronnstrand, L., Cheifetz, S., and Massa- 
gue, J. 1991. Purification of the transforming 
growth factor-|8 (TGF-|8) binding proteoglycan 
betaglycan. /5zo/ Chem 266:23282-23287. 
Attisano, L., Wrana, J.L., Cheifetz, S., and Massague, 
J. 1992. Novel activin receptors: distinct genes 
and alternative mRNA splicing generate a reper- 
toire of serine/threonine kinase receptors. Cell 
68:97-108. 
Cheifetz, S., and Massague, J. 1991. Isoform- 
specific transforming growth factor-/? binding 
proteins with membrane attachments sensitive to 
phosphatidylinositol-specific phospholipase C.J 
Biol Chem 266:20767-20772. 
Lidholt, K., Weinke, J. L., Kiser, C.S., Lugemwa, F.N., 
Bame, K.J., Cheifetz, S., Massague, J., Lindahl, 
U., and Esko, J.D. 1992. A single mutation affects 
both A'-acetylglucosaminyltransferase and glucur- 
onosyltransferase activities in a Chinese hamster 
ovary cell mutant defective in heparan sulfate bio- 
synthesis. Proc Natl Acad Sci USA 89:2267- 
2271. 
Lopez-Casillas, F., Cheifetz, S., Doody, J., Andres, 
J.L., Lane, W.S., and Massague, J. 1991. Structure 
and expression of the membrane proteoglycan be- 
taglycan, a component of the TGF-|8 receptor sys- 
tem. Ce// 67:785-795. 
Massague, J. 1992. Receptors for the TGF-(8 family. 
Ce// 69:1067-1070. 
Massague, J., Andres, J., Attisano, L., Cheifetz, S., 
Lopez-Casillas, F., Ohtsuki, M., and Wrana, J.L. 
1992. TGF-/3 receptors. Mol Reprod Dev 32:99- 
104. 
Massague, J., Cheifetz, S., Laiho, M., Ralph, D.A., 
Weis, F.M.B., and Zentella, A. 1992. Transform- 
ing growth factor-/3. Cancer Surv 12:81-104. 
Massague, J., and Weinberg, R.A. 1992. Negative 
regulators of growth. Curr Opin Genet Dev 
2:28-32. 
Ohtsuki, M., and Massague, J. 1992. Evidence for 
the involvement of protein kinase activity in 
transforming growth factor-/? signal transduction. 
Mol Cell Biol 12:261-265. 
Zentella, A., and Massague, J. 1992. Transforming 
growth factor-j8 induces myoblast differentiation 
in the presence of mitogens. Proc Natl Acad Sci 
USA 89:5176-5180. 
Zentella, A., Weis, F.M.B., Ralph, D.A., Laiho, M., 
and Massague, J. 1991. Early gene responses to 
transforming growth factor-jS in cells lacking 
growth-suppressive RB function. Mol Cell Biol 
11:4952-4958. 
TRANSCRIPTIONAL REGULATORY PROTEINS 
Steven L. McKnight, Ph.D., Investigator 
During the past year Dr. McKnight's laboratory 
has focused on the terminal differentiation of adi- 
pose cells. More than a decade ago Dr. Howard 
Green isolated a line of cultured mouse cells that 
could be induced to differentiate from a prolifera- 
tive, fibroblastic phenotype into fat-laden adipo- 
cytes. The differentiation process undertaken by 
these 3T3-L1 cells was determined by empirical 
methods to be regulated by three hormonal in- 
ducers: insulin, dexamethasone, and methylisobu- 
tylxanthine (a phosphodiesterase inhibitor). When 
exposed to this hormonal cocktail, otherwise prolif- 
erative 3T3-L1 cells initiate a differentiation pro- 
gram that culminates in the arrest of mitotic growth 
CELL BIOLOGY AND REGULATION 95 
