Cesari R, Martin ES, Calin GA, Pentimalli F, Bichi R, McAdams H, Trapasso F, Drusco A, Shimizu M, Masciullo V, D'Andrilli G, Scambia G, Picchio MC, Alder H, Godwin AK, Croce CM. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5956-61. PubMed.
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Massachusetts General Hospital
These findings represent an intriguing potential convergence with our own data (see ARF related news story), which demonstrated that parkin forms a ubiquitin ligase complex that downregulates cyclin E. Cyclin E has been shown to accumulate in some mammary tumors (Keyomarsi et al., 2002), and hSel-10/Cdc4, which we have shown to be a part of the parkin complex, is sporadically mutated in at least one breast cancer line (Strohmaier et al., 2001). Clearly, an important next step is to look at cyclin E expression at the mRNA and protein levels in tumors with loss of heterozygosity linked to the parkin locus. Perhaps parkin mutations and cyclin E accumulation are double-edged swords, leading to neurodegeneration in some cases and to cancer in others.
References:
Keyomarsi K, Tucker SL, Buchholz TA, Callister M, Ding Y, Hortobagyi GN, Bedrosian I, Knickerbocker C, Toyofuku W, Lowe M, Herliczek TW, Bacus SS. Cyclin E and survival in patients with breast cancer. N Engl J Med. 2002 Nov 14;347(20):1566-75. PubMed.
Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001 Sep 20;413(6853):316-22. PubMed.
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