TSG101

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Gene: maps to .
mRNA: size:
Protein: a 46-kDa. TSG101 interacts with stathmin/oncoprotein 18, a 19-kDa cytosolic protein that becomes phophorylated in response to diverse signals associated with cell growth and differentiation. The presence of a carboxyterminal leucine-zipper containing a leucin heptad repeat (coiled-coil) domain and an amino terminal prolie-rich region consistent with a transactivation domain have suggested that one of the functions of TSG101 may be to modulate or mediate transcription. TSG101 was shown to interact with p300 and to repress androgen- and estrogen-receptor transactivation (Sun Z. et al., 1999). Structural analysis of TSG101 also has led to proposals that it could function as a regulator of ubiquitination or a protector from DNA damage (Ponting C.P. et al., 1997; Thomson T.M. et al., 1998).
The expression level of TSG101 is not cell cycle dependent. However, it may relocalize from the cytoplasm to the nucleus from G₁ to S phase. TSG101 is mainly distributed surrounding the chromosomes during M phase. Microinjection of both polyclonal and monoclonal antibodies specific to TSG101 into cells during G1 or S phase results in cell cycle arrest. Furthermore, overexpression of TSG101 leads to cell death, suggesting that the appropriate amount of TSG101 is critical for cell cycle progression. Neoplastic transformation caused by TSG101 deficiency may result from bypassing of the cell cycle checkpoints (Zhong Q. et al., 1998).

Cell lines:
- Full-size 46-kDa TSG101 mRNA and protein were found in MCF-7, T-47D, BT-483, SKBR3, ZR-75, -175-VII, -231, -361, -435, and -468 breast cancer cell (BCC) lines. TSG101 mRNA was also found in BT-474, MDA-MB-134-VI, -436, -453, and -436 BCC lines. In T-47D TSG101 mRNA and protein were much lower than in other BCC lines (Zhong Q. et al., 1997).

Tumors:

Ponting C.P. et al. (1997) The breast cancer gene product TSG101: a regulator of ubiquitination? J. Mol. Med. 75, 467-469.
Sun Z. et al. (1999) Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300. Cancer 86, 689-696.
Thomson T.M. et al. (1998) Role of UEV-1A, a homologue of the tumor suppressor protein TSG101, in protection from DNA damage. FEBS Lett. 423, 49-52.
Zhong Q. et al. (1997) Identification of cellular TSG101 protein in multiple human breast cancer cell lines. Cancer Res. 57, 4225-4228.
Zhong Q. et al. (1998) Perturbation of TSG101 protein affects cell cycle progression. Cancer Res. 58, 2699-2702.

Under construction