The decision may deepen Nawaz Sharif's rift with the ruling PPP
Pakistan's Supreme Court has upheld bans on former prime minister and opposition leader Nawaz Sharif and his brother, Shahbaz, from elected office.
Nawaz Sharif's PML-N party holds power in Punjab province. His brother is chief minister but must now step down.
Nawaz Sharif accused President Asif Ali Zardari of being behind the ban.
Mr Sharif said it was because he would not back down in his campaign to have judges sacked by ex-president Pervez Musharraf reinstated.
The BBC's Barbara Plett in Islamabad says that the court order will deepen the rift between the Sharifs and the federal government and increase the chances of political instability in the country.
Last June, the high court in the city of Lahore upheld an earlier ruling that barred Nawaz Sharif from running in a parliamentary by-election. The court said he was ineligible to stand because of a 1999 conviction.
Ahsan Iqbal from the PML-N party says the party remains committed to independence
One of the Sharif lawyers, Akram Sheikh, confirmed that their latest appeal in the Supreme Court had been dismissed.
Nawaz Sharif said Mr Zardari was behind the ban as the president opposed his stance on the judges.
Nawaz Sharif said the president had offered a deal to resolve the issue last month in a meeting with his brother.
"You give up your campaign against the judges and they will rule that you are eligible," Mr Sharif said his brother was told by the president.
Mr Sharif said Shahbaz Sharif immediately refused the offer, but "we choose to keep it secret till now".
Mr Zardari has made no comment yet on the allegation.
Mr Sharif said the latest ruling would not change his policy and called for a nationwide protest against the court ruling on Thursday.
President Zardari had a hand in the decision, Nawaz Sharif believes
Nawaz Sharif is not an MP at the moment, but analysts say the court order will force Shahbaz Sharif to step down from the post of Punjab's chief minister.
Nawaz Sharif had been convicted in connection with the 1999 hijacking of a plane carrying then army chief Gen Pervez Musharraf.
The event led to Gen Musharraf ousting Mr Sharif in a coup and going on to become president.
Nawaz Sharif had returned from exile, hoping his ban from office would be lifted by a democratically elected government.
The PML-N and Pakistan's ruling party PPP then emerged as the two biggest parties after last year's elections, trouncing allies of Pervez Musharraf.
They formed a fragile coalition and managed to force Mr Musharraf out of office.
But soon after, Mr Sharif fell out with the PPP leader, Mr Zardari, and they split over the issue of the reinstatement of the judges.
Our correspondent, Barbara Plett, says the latest ruling raises fears of a return to the bitter political infighting that characterised elected governments in the 1990s, now though, at a time when Pakistan is facing security and economic crises.
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