Three steps to cancer: how phosphorylation of tubulin, tubulin tyrosine ligase and P-glycoprotein may generate and sustain cancer.
Transformed cells progress to cancer because they are not eliminated by apoptosis. In this brief minireview I propose, based on published data, that the cell possesses a 'last check point' (LCP) apoptotic step in the form of assembly of nitrotyrosinated alpha-tubulin onto microtubules. This leads to microtubule dysfunction and ultimately apoptosis. I also propose that cells that escape this LCP apoptotic step develop into cancer. Phosphorylation of tubulin tyrosine ligase (TTL) is postulated to cause escape from LCP apoptosis. Phosphorylation also ensures that cancer cells survive a hostile milieu (e.g. chemotherapy).
Idriss
Haitham T
HT
Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th St, 904, BLSB, Philadelphia, PA 19107-5541, USA. h_idriss@mail.jci.tju.edu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D018432:Drug Resistance, Multiple; D006801:Humans; D008870:Microtubules / Q000502:physiology*; D009369:Neoplasms / Q000503:physiopathology; D010453:Peptide Synthases / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D014404:Tubulin / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014404:Tubulin; D010453:Peptide Synthases; C023213:tyrosyltubulin ligase