True statements about P53 gene are all except ?
Arrest cell cycle at GI Phase
Product is 53 KD protein
Located on chromose 17
Wild/non-mutated form is associated with increased risk of childhood tumors.
It is mutated form (not non mutated form) of p53 which is associated with increased risk of tumors. o p53 gene is a tumor suppressor gene and non-mutated form of this gene prevent development of malignancy by : (i) Causing cell cycle arrest in late GI phase (ii) Inducing apoptosis (iii) Helping in DNA repair o Mutation in p53 gene causes inactivation of p53 gene and abolishen of above function that results in uncontrolled proliferation of cells and malignant transformation. o Mutation in p53 gene is the most common genetic alteration found in human Cancer. o The name p53 is in reference to its apparent molecular mass; it runs as a 53 kilodalton (Kda) protein on SDS-page. But based on calculations from its amino acid residues, p53 's mass is actually only 43.7 K Da. o p53 prevents neoplastic transformation by three interlocking mechanisms : ? 1. Activation of temporary cell cycle arrest (quiescence) o It is considered as the primordial response to DNA damage. o p53 causes arrest in late GI through p2 I . o This is temporary arrest that gives the cell "breathing time" to repair DNA damage. o After DNA repair, cell cycle block is relieved by MDM-3 which degrades p53. 2. Induction of permanent cell cycle arrest (senescence) o p53 induced sencence is a permanent cell cycle arrest characterized by specific changes in morphology and gene expression that differentiate it from quiescence (temporary or reversible cycle arrest). o The mechanisms of senscence is unknown, but involve epigenetic changes that result in the formation of heterochromatin at different loci throughout the genome. 3. Triggering of programmed cell death o p53 directs the transcription of several pro-apoptotic genes such as BAX and PUMA (approved name BBC3) and induces apoptosis. o It has been shown that p53 activates transcription of the mir 34 family of micro RNAs (miRNAs),mir 34a. o mir34 inhibits translation of anti-apoptotic genes such as BCL2 (there by induce apoptosis) and pro-proliferative genes such as cyclins (there by prevent proliferation) p53 induce apoptosis and prevent proliferation through mir34.