SMAR1-derived P44 peptide retains its tumor suppressor function through modulation of p53

Jalota-Badhwar, Archana ; Kaul-Ghanekar, Ruchika ; Mogare, Devraj ; Boppana, Ramanamurthy ; Paknikar, Kishore M. ; Chattopadhyay, Samit (2007) SMAR1-derived P44 peptide retains its tumor suppressor function through modulation of p53 The Journal of Biological Chemistry, 282 (13). pp. 9902-9913. ISSN 0021-9258

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The use of pharmacologically active short peptide sequences is a better option in cancer therapeutics than the full-length protein. Here we report one such 44-mer peptide sequence of SMAR1 (TAT-SMAR1 wild type, P44) that retains the tumor suppressor activity of the full-length protein. The protein transduction domain of human immunodeficiency virus, type 1, Tat protein was used here to deliver the 33-mer peptide of SMAR1 into the cells. P44 peptide could efficiently activate p53 by mediating its phosphorylation at serine 15, resulting in the activation of p21 and in effect regulating cell cycle checkpoint. In vitro phosphorylation assays with point-mutated P44-derived peptides suggested that serine 347 of SMAR1 was indispensable for its activity and represented the substrate motif for the protein kinase C family of proteins. Using xenograft nude mice models, we further demonstrate that P44 was capable of inhibiting tumor growth by preventing cellular proliferation. P44 treatment to tumor-bearing mice prevented the formation of poorly organized tumor vasculature and an increase in hypoxia-inducible factor-1α expression, both being signatures of tumor progression. The chimeric TAT-SMAR1-derived peptide, P44, thus has a strong therapeutic potential as an anticancer drug.

Item Type:Article
Source:Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
ID Code:60236
Deposited On:08 Sep 2011 09:34
Last Modified:08 Sep 2011 09:34

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