Synthetic Lethality Induced By Loss of PKC d And Mutated Ras  

Oleh:

Zhu, Tongbo ; Chen, Lihua ; Tsuji, Takanori ; Chen, Changyan

Jenis: Article from Article
Dalam koleksi: Genes and Cancer vol. 1 no. 2 (May 2010), page 142-151.
Topik: PKC; JNK; RACK1; Ras; Synthetic Lethality
Fulltext: 142.full.pdf (574.7KB)

Isi artikel

Synthetic lethal interaction between oncogenic Ha-ras and loss of PKC has been demonstrated. Recently, the authors reported that the concurrent knockdown of PKC a and ß, via upregulating PKC d, sensitizes cells with aberrant Ras signaling to apoptosis. As a continuation of the study, using shRNA, the authors demonstrate that loss of PKC d causes a lethal reaction in NIH3T3/Hras or prostate cancer DU145 cells that overexpress JNK. In this apoptotic process, PKC a and ß are upregulated and then associated with RACK1 (an adaptor for activated PKC) and JNK. Immunoblotting analysis shows that JNK is phosphorylated, accompanied with caspase 8 cleavage. The inhibition of JNK abrogates this apoptotic process triggered by PKC d knockdown. Interestingly, without blocking PKC d, the concurrent overexpression of wt- or CAT-PKC a and ß is insufficient to induce apoptosis in the cells. Together with the authors’ previous findings, the data suggest that PKC a/ß and d function oppositely to maintain a balance that supports cells expressing v-ras to survive and prevents them from being eliminated through oncogenic stress-induced apoptosis.

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