Search for directed genic interactions:  

BCL2 MTOR (1 - 1 of 1)
PMID: 15208671
Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt.
Bcl-2 phosphorylation ... microtubules require mTOR and ...   (details)

BCL2 MTOR

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 15208671

Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt.
Source

Oncogene (7/29/2004)

Abstract

Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt. The serine/threonine kinase mTOR, the major sensor of cell growth along the PI3K/Akt pathway, can be activated by agents acting on microtubules. Damaged microtubules induce phosphorylation of the Bcl-2 protein and lower the threshold of programmed cell death, both of which are inhibited by rapamycin. In HEK293 cells expressing Akt mutants, the level of Bcl-2 phosphorylation and the threshold of apoptosis induced by taxol or by nocodazole are significantly modified. In cells expressing dominant-negative Akt (DN-Akt), Bcl-2 phosphorylation and p70S6KThr421/Ser424 phosphorylation induced by taxol or nocodazole were significantly enhanced as compared to cells expressing constitutively active Akt (CA-Akt) and inhibited by rapamycin. Moreover, DN-Akt cells were more sensitive to antitubule agents than CA-Akt cells. In nocodazole-treated HEK293 cells sorted according to cell cycle, the p70S6KThr421/Ser424 phosphorylation was associated to the G2/M fraction. More relevant, nocodazole inhibited, in a dose-response manner, mTOR phosphorylation at Ser2448. This activity, potentiated in DN-Akt cells, was not detectable in CA-Akt cells. Our results suggest that death signals originating from damaged microtubules in G2/M can compete with G1 survival pathways at the level of mTOR. These findings have implications for cancer therapy and drug resistance.